The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index; none of the 14 sources its claims cite is checked for support yet.
A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis
Open accessAbstract
The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.
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“R207910 was extensively distributed to tissues, including lungs and spleen (Fig. 3A, table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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“These average concentrations were greater than that achieving optimal activity in established infection in mice.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
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In the paper
“Low MICs were also found for other mycobacterial species, including Mycobacterium bovis, Mycobacterium kansasii and Mycobacterium ulcerans, as well as species naturally resistant to many other anti-TB agents and involved in opportunistic infections, such as Mycobacterium avium complex (MAC), Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium marinum (Table 1).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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In the paper
“At 25 mg/kg, the activity of R207910 was significantly better than at 12.5 mg/kg (P = 0.005).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
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In the paper
“The bactericidal activity obtained by the RHZ combination after 2 months of therapy was matched by the combinations JHZ and RJZ after just 1 month of therapy.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
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In the paper
“Importantly, at 12.5 and 25 mg/kg, R207910 was significantly more active (P = 0.005) than 25 mg/kg isoniazid, a drug known for its strong, early bactericidal activity (Fig. 4A).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
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In the paper
“In addition, the susceptibility of R207910-resistant M. tuberculosis strains remained unchanged to other anti-TB agents, including isoniazid, rifampin, streptomycin, amikacin, ethambutol and moxifloxacin.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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“To date, 20 molecules of the DARQ series have a minimum inhibitory concentration (MIC) below 0.5 µg/ml against M. tuberculosis H37Rv.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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“Data from a multiple-ascending-dose study have shown an increase (approximately by a factor of two) in AUC 0-24h from Day 1 to Day 14 of once-daily dosing at 50, 150 and 400 mg R207910, without substantial variation between subjects.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Plasma levels associated with efficacy in mice are well tolerated in healthy human volunteers.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 3
- It may state two separate claims as one. 40
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In the paper
“The most active compound of the class, R207910, is a pure enantiomer with two chiral centers.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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“No accumulation of R207910 was observed after five daily oral doses, indicating that slow redistribution from tissues contributed to the relatively long half-lives in plasma.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgeddirect- Asserted: passes — The authors put it forward as true.
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“In the second study, the good tolerability was maintained; only one subject withdrew from the study, because of a urinary tract infection (unrelated to R207910) after seven doses at 150 mg/day.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plainSingle case- Asserted: passes — The authors put it forward as true.
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“When added to the first-line triple TB therapy combination RHZ, 25 mg/kg R207910 (J) increased the drop in bacterial load in the lungs by 2 log 10 after 1 month of therapy compared with standard RHZ treatment regimen, and a further 1 log 10 drop after 2 months.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
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In the paper
“Maximum plasma concentrations (C max ) of 0.40-0.54µg/ml with a single 6.25 mg/kg/dose were achieved within 1 hour and 1.1-1.3µg/ml with a 25 mg/kg/dose within 2-4 hours.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaindirect- Asserted: passes — The authors put it forward as true.
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“The majority of adverse events reported (supporting online text), were considered possibly related to the study medication-placebo (seven of 18 subjects) or R207910 (20 of 36 subjects).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plainconditionaln = 36- Asserted: passes — The authors put it forward as true.
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“The AUC showed a better correlation with the dose than C max , reflecting limitations in rate of absorption at higher dosing regimens, as confirmed in a single-dose pharmacokinetic study comparing C max and AUC after 6.25, 25 and 100 mg/kg.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This anti-mycobacterial-specific spectrum differs from that of isoniazid, which has very poor activity against MAC.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In studies using oral treatment of R207910 for 5 days per week for 4 weeks, starting the day after inoculation, the minimal dose of R207910 that prevented mortality in nonestablished infection was 1.5 mg/kg, and the minimal effective dose (MED) preventing gross lung lesions was 6.5 mg/kg.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Exposure of M. tuberculosis in log-phase growth to concentrations of R207910 at 10-fold MIC resulted in a 3 log 10 reduction in bacterial counts after 12 days, indicating that R207910 has bactericidal activity in vitro (table S2).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Complementation studies have verified that the mutant atpE gene is responsible for resistance to R207910, implying that the atpE gene product is the target of R207910 in mycobacteria.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The range of MICs for the international reference strain M. tuberculosis H37Rv and six fully antibiotic susceptible isolates was 0.03-0.120µg/ml (Table 1), versus 0.500 µg/ml for rifampin and 0.120 µg/ml for isoniazid (results not shown).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“All 30 isolates of MDR-TB tested were susceptible to 0.100 µg/ml of R207910, and 17 (57%) were susceptible to 0.010 µg/ml of R207910 (Table 2).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Pharmacokinetic results from the single-ascending-dose study suggested that R207910 is well absorbed after single oral administration, and the peak concentration was reached at 5 hours (median value) post-dose.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“R207910 had much higher MICs for Corynebacterium and Helicobacter pylori (MIC 4.0 µg/ml), and especially for other organisms such as Gram-positive Nocardia, Streptococcus pneumoniae, Staphylococcus aureus and Enterococcus faecalis, or Gram-negative Escherichia coli and Haemophilus influenzae (table S1).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Half-lives ranged from 43.7 to 64 hours in plasma and 28.1 to 92 hours in tissues (table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Substitution of drugs included in the World Health Organization's firstline tuberculosis treatment regimen (rifampin, isoniazid and pyrazinamide) with R207910 accelerates bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The DARQ R207910 is a member of a new chemical class of anti-mycobacterial agents and has an MIC equal to or lower than that of reference compounds.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“A single dose of 50 mg/kg R207910 in the non-established infection murine model of TB infection resulted in a bacteriostatic effect (0.5 log 10 drop in bacterial count in the lungs), which lasted for 8 days-a similar effect to that of rifapentine (10 mg/kg) (Fig. 3B).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In established infection (treatment beginning 12-14 days after inoculation when bacterial load was 5.94 log 10 CFU), 25 mg/kg R207910 as monotherapy was at least as active as the triple combination therapy (rifampin [R] + isoniazid [H] + pyrazinamide [Z]), and more active than rifampin alone (Fig. 4B).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (MIC 0.06 µg/ml).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The mean AUC 0-24h values were 7.91, 24 and 52 µg/hour/ml at steady state, corresponding to average concentrations of 0.33, 1.0 and 2.2 µg/ml across a dosing interval, with 50, 150 and 400 mg/day, respectively.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The pharmacokinetics of R207910 were linear up to the highest dose tested (700 mg); both C max and AUC increased proportionally with the administered dose.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The two point mutations identified (D32V for M. smegmatis and A63P for M. tuberculosis) are both in the membrane-spanning domain region of the protein.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Areas under the concentration-time curve (AUCs) ranged from 5.0 to 5.9 µg/hour/ml with a 6.25 mg/kg/dose and 18.5 to 19.4 µg/hour/ml with a 25 mg/kg/dose (table S4).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
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In the paper
“From selection experiments, the proportion of resistant mutants that emerged was 5 x 10 -7 and 2 x 10 -8 at four-fold MIC, and 5 x 10 -8 and 1 x 10 -8 at eight-fold MIC for M. tuberculosis and M. smegmatis, respectively (8).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
What the sources say
- Not matchedcites [8] 8. Details of materials and methods and supporting online text are available as supporting material on Science Online.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“Substitution of each of the three first-line drugs with R207910 resulted in a dramatic increase in potency, leading to complete culture conversion of the lungs in some animals after only 2 months of treatment.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“R207910 has potent early bactericidal activity in the nonestablished murine TB model, matching or exceeding that of isoniazid (Fig. 4A), which is consistent with in vitro observations pointing to a bactericidal activity.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, the bactericidal potency seen upon administration of a single dose of 100 mg/kg R207910 in vivo was similar to the effect seen upon continuous exposure of cultures to 0.6 µg/ml (or 10-fold the median MIC of the H37Rv strain) in vitro, giving a first indication of the pharmacodynamics of R207910.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the minimal bactericidal dose was very close to the MED, a finding confirming timedependent, rather than concentration-dependent, activity of R207910 in vitro.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Pharmacodynamic studies in mice.
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Data suggest that maintaining average plasma levels of 0.3 µg/ml/day across a dosing interval, which is achieved with a 100 mg/kg/week dose, is necessary to achieve optimal effect of monotherapy in mice infected with strain H37Rv.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The killing effect was not increased by higher concentrations of the compound, suggesting the killing was time-dependent rather than concentration-dependent.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Although current first-line anti-TB drug regimens can achieve more than 99% efficacy, this is often reduced because of drug resistance (5).”
What the sources say
- Not matchedcites [5] 5. R. J. O'Brien, P. P. Nunn, Am. J. Respir. Crit. Care Med. 163, 1055 (2001).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
- Not matched
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Structurally and mechanistically, DARQs are very different from both fluoroquinolones (including methoxyquinolones) and other quinoline classes, including mefloquine and its analogs 4-methylquinolines and 4quinolylhydrazones (9-13).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
What the sources say
- Not matchedcites [9] 9. R. Jain, B. Vaitilingam, A. Nayyar, P. B. Palde, Bioorg. Med. Chem. Lett. 13, 1051 (2003).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [10] 10. C. M. Kunin, W. Y. Ellis, Antimicrob. Agents Chemother. 44, 848 (2000).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [11] 11. M. R. Barbachyn, S. J. Brickner, Patent (International Publication Number: WO 93/09103, International Publication Date: 13 May, 1993, International Application Number: PCT/US92/08267, International Filing Date: 1992).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [12] 12. L. Savini, L. Chiasserini, A. Gaeta, C. Pellerano, Bioorg. Med. Chem. 10, 2193 (2002). / www.sciencexpress.org /9 December 2004 / Page 4/ 10.1126/science.1106753
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [13] 13. S. Vangapandu, M. Jain, R. Jain, S. Kaur, P. P. Singh, Bioorg. Med. Chem. 12, 2501 (2004).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The long half-lives and consequently prolonged exposure are important factors determining the duration of activity in vivo and provide a rationale for less frequent dosing regimens.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Chemistry and in vitro anti-mycobacterial activity.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A comparison of the sequences of ATP synthases of different bacteria and of eukaryotic ATP synthase provides a rationale for the specificity of the antibacterial spectrum and, to a lesser extent, the safety profile of R207910.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, the distinct target of R207910 means that there is no crossresistance with existing anti-TB drugs, and our studies verified it is as effective against MDR strains as it is against fully antibiotic-susceptible strains.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Inhibition of ATP synthase function may lead to ATP depletion and imbalance in pH homeostasis, both contributing to decreased survival (15,16).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
What the sources say
- Not matchedcites [15] 15. M. Rao, T. L. Streur, F. E. Aldwell, G. M. Cook, Microbiology 147, 1017 (2001).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [16] 16. G. Deckers-Hebestreit, K. Altendorf, Annu. Rev. Microbiol. 50, 791 (1996).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These are all attributes that are valuable for treatment of chronic infections and they may also be important for the development of simpler dosing regimens.”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“The extent of bacterial load, the most effective drug combinations and treatment duration needed for sterilization are all similar in mice and humans (17).”
§ A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis > Safety and tolerability in humans.
What the sources say
- Not matchedcites [17] 17. E. L. Nuermberger et al., Am. J. Respir. Crit. Care Med. 169, 421 (2004).
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Not matched
The paper relies on this without support.
No tuberculosis-specific drugs have been discovered in 40 years.
“Tuberculosis has been increasing significantly on a worldwide basis over the past decade, but no tuberculosisspecific drugs have been discovered in 40 years.”
The paper relies on this without support.
The murine TB model is predictive of human TB treatment outcomes.
“The extent of bacterial load, the most effective drug combinations and treatment duration needed for sterilization are all similar in mice and humans (17).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“TMC207 is bactericidal towards most species of mycobacteria (109), but is only bacteriostatic against M. avium (118) and M. smegmatis (Berney and Cook, unpublished data).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When mycobacterial cells (growing or non-growing) are treated with TMC207, time-dependent (not dose-dependent) killing is observed (109).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The most promising compounds clinically, the diarylquinolines, have been shown to target the F1Fo-ATP synthase and inhibit ATP synthesis (109, 111, 112).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [109]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“M. smegmatis was used for the initial compound screening that identified diarylquinoline (later named Bedaquiline) as a specific inhibitor of mycobacterial ATP synthase in 2005, which ended a 40-year dearth in anti-TB drug discovery (147).”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [147]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Furthermore, Bedaquiline, the first new TB drug in 40 years, was discovered through an M. smegmatis screen.”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [147]
Citations
Cites
Amino acid substitution matrices from protein blocks.
Henikoff, S., & Henikoff, J. G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10915 · Cited by 6,218
The Growing Burden of Tuberculosis: Global Trends and Interactions With the HIV Epidemic
Corbett, E. L., Watt, C. J., Walker, N., Maher, D., Williams, B. G., Raviglione, M. C., & Dye, C. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1009 · Cited by 2,553
A systematic review of the associations between dose regimens and medication compliance
Claxton, A. J., Cramer, J., & Pierce, C. (2001) · Clinical Therapeutics · doi:10.1016/s0149-2918(01)80109-0 · Cited by 2,388
Comparing the Means of Several Groups
Godfrey, K. (1985) · New England Journal of Medicine · doi:10.1056/nejm198512053132305 · Cited by 740
Moxifloxacin-containing Regimen Greatly Reduces Time to Culture Conversion in Murine Tuberculosis
Nuermberger, E. L., Yoshimatsu, T., Tyagi, S. K., et al. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200310-1380oc · Cited by 315
Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis
Siddiqi, S. H., Libonati, J. P., & Middlebrook, G. (1981) · Journal of Clinical Microbiology · doi:10.1128/jcm.13.5.908-912.1981 · Cited by 242
The Need for New Drugs against Tuberculosis
O'BRIEN, R. J., & NUNN, P. P. (2001) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.163.5.2007122 · Cited by 221
THE F0F1-TYPE ATP SYNTHASES OF BACTERIA: Structure and Function of the F0 Complex
Deckers-Hebestreit, G., & Altendorf, K. (1996) · Annual Review of Microbiology · doi:10.1146/annurev.micro.50.1.791 · Cited by 195
Intracellular pH regulation by Mycobacterium smegmatis and Mycobacterium bovis BCG
Rao, M., Streur, T. L., Aldwell, F. E., & Cook, G. M. (2001) · Microbiology · doi:10.1099/00221287-147-4-1017 · Cited by 148
Synthesis and anti-tubercular evaluation of 4-quinolylhydrazones
Savini, L., Chiasserini, L., Gaeta, A., & Pellerano, C. (2002) · Bioorganic & Medicinal Chemistry · doi:10.1016/s0968-0896(02)00071-8 · Cited by 134
Cited by
Sorted by citations
Items 1,701–1,800 of 2,159
Kauffman, J., Cuevas, J., Feiner, J., et al. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.117531 · Cited by 3
Pandey, S. K., Lavu, E., Congdon, J., et al. (2018) · Tuberculosis · doi:10.1016/j.tube.2018.06.006 · Cited by 3
Turbine enzyme’s structure in the crosshairs to target tuberculosis
Duncan, T. M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1900798116 · Cited by 3
Fekadu, G., Yao, J., & You, J. H. S. (2021) · Expert Review of Pharmacoeconomics & Outcomes Research · doi:10.1080/14737167.2021.1925111 · Cited by 3
Immunotherapy of Tuberculosis with IgA and Cytokines
Reljić, R., & Iványi, J. (2012) · InTech eBooks · doi:10.5772/30495 · Cited by 3
“Although new drugs have been proposed for treatment [1], the need for new therapies is of major concern in the fight against the MDR-TB.”
BackgroundGuillemont, J., Meyer, C., Koul, A., & Andries, K. (2012) · Elsevier eBooks · doi:10.1016/b978-0-08-095167-6.00107-5 · Cited by 3
Self-citation3,4-Dimethoxybenzaldehyde [2,8-bis(trifluoromethyl)quinolin-4-yl]hydrazone
Al-Eryani, W. F. A., Kumari, J. S., Arunkashi, H. K., et al. (2010) · Acta Crystallographica Section E Structure Reports Online · doi:10.1107/s1600536810021616 · Cited by 3
“Quinoline is the essential structural feature found in mefloquin and recently developed antimycobacterial drugs (Andries et al. 2005).”
BackgroundRespiration and Oxidative Phosphorylation in Mycobacteria
Berney, M., & Cook, G. M. (2014) · Advances in photosynthesis and respiration · doi:10.1007/978-94-017-8742-0_15 · Cited by 3
Ahmad, Z., Dadi, P. K., Elord, J., & Kady, I. O. (2012) · Advances in Biological Chemistry · doi:10.4236/abc.2012.22019 · Cited by 3
“cobacterium ATP synthase in conferring resistance against the anti-tuberculosis drug diarylquinoline [20], all indicate a strong need for more potent inhibitors of bacterial ATP synthase.”
BackgroundDrug Discovery for TB: Frontiers and Perspectives
(2014) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9781608059126114030003 · Cited by 3
Recently Disclosed Chemical Entities As Potential Candidates for Management of Tuberculosis
Stec, J., & Abourashed, E. A. (2015) · Pharmaceutical Patent Analyst · doi:10.4155/ppa.15.13 · Cited by 3
Antitubercular drug discovery: the molecular modification as promise tool
Dutra, L. A., de Melo, T. R. F., Chin, C. M., & dos Santos, J. L. (2012) · Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) · Cited by 3
Elliott, R. (2011) · Topics in medicinal chemistry · doi:10.1007/978-3-642-23487-3 · Cited by 3
Olurotimi, O. K., Adeyemi, A. J., Agbeke, B. O., et al. (2017) · Oriental Journal Of Chemistry · doi:10.13005/ojc/330405 · Cited by 3
Design, synthesis, and antitubercular activity of 3‐amidophenols with 5‐heteroatomic substitutions
Zhang, N., Tang, Y., Qian, L., et al. (2019) · Archiv der Pharmazie · doi:10.1002/ardp.201800277 · Cited by 3
Maurady, A., M’guil, M., Sadoq, B., Eslami, G., & Britel, M. R. (2022) · Advances in intelligent systems and computing · doi:10.1007/978-3-030-90633-7_15 · Cited by 3
CHOUAID, C. (2006) · Revue des Maladies Respiratoires · doi:10.1016/s0761-8425(06)72006-x · Cited by 3
Gbala, I., Macharia, R. W., Bargul, J. L., & Magoma, G. N. (2022) · Microbiology Spectrum · doi:10.1128/spectrum.02062-22 · Cited by 3
Two Steps Forward, One Step Back
Diacon, A. H. (2022) · New England Journal of Medicine · doi:10.1056/nejme2214707 · Cited by 3
Omel'kov, A. V., Fedorov, V. E., & Степанов, А. А. (2019) · Russian Chemical Bulletin · doi:10.1007/s11172-019-2646-5 · Cited by 3
Resource misallocation as a mediator of fitness costs in antibiotic resistancePreprint
Trauner, A., Banaei‐Esfahani, A., Gygli, S. M., Warmer, P., Feldmann, J., Shafieechashmi, S., Eschbach, K., Zampieri, M., Borrell, S., Collins, B. C., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/456434 · Cited by 3
Maeda, M. (2010) · YAKUGAKU ZASSHI · doi:10.1248/yakushi.130.191 · Cited by 3
Srinivas, V., Ruiz, R. A., Pan, M., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.09.430468 · Cited by 3
Mathiyazakan, V., Kathalingam, S. S., Pok, W. N., et al. (2025) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5c00092 · Cited by 2
Bedaquiline Activity against Leprosy
Fomba, A., Haidara, F. C., Kodio, M., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmc2412487 · Cited by 2
Self-citationMaghradze, N., Loiseau, C., Goig, G. A., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0326794 · Cited by 2
“This includes bedaquiline (BDQ), a novel class of anti-mycobacterial medication with a high potency [1] that has led to substantially improved treatment outcomes among persons with drug-resistant tuberculosis (DR-TB) [2].”
Tiwari, S., Nain, V. K., Ahmad, M., Kumar, V. S., Kar, D., Kumari, S., Dwivedy, A., Pal, R. K., Mohapatra, A. K., Barik, V., et al. (2025) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5c00393 · Cited by 1
Huang, F. F., Shi, M., Liu, C., Li, X., Wang, Z., Jiang, D. H., Chen, J.-F., Zhang, H., & He, Z. (2025) · Communications Biology · doi:10.1038/s42003-025-09107-3 · Cited by 4
Collateral sensitivity and genetic vulnerability of antibiotic resistance
Yang, K. B., Rasouly, A., & Nudler, E. (2025) · Trends in Microbiology · doi:10.1016/j.tim.2025.11.002 · Cited by 2
Essential redundancies fuel Mycobacterium tuberculosis adaptation to the host
Silva, M., Pinto, A. J., & Beites, T. (2025) · PLoS Pathogens · doi:10.1371/journal.ppat.1013749 · Cited by 2
“In oxidative phosphorylation, the most well-known example in M. tuberculosis is ATP synthase – the target of bedaquiline, a drug that revolutionized the treatment of drug-resistant TB [114,115].”
Mycobacterial respiratory chain enzymes and growth are inhibited by decylubiquinone
Król, S. K., Kovaĺová, T., Janczak, M., Kalsum, S., Akber, M., Högbom, M., Brighenti, S., Ädelroth, P., & Brzezinski, P. (2025) · Communications Biology · doi:10.1038/s42003-025-09309-9 · Cited by 2
Park, J., Choi, S. H., Jeon, Y. R., et al. (2025) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01511-25 · Cited by 2
We Are Underprepared for Bedaquiline Resistance: A Call for Clinical and Programmatic Readiness
Cross, G. B., Walker, H. N., Hasan, T., et al. (2026) · Clinical Infectious Diseases · doi:10.1093/cid/ciag008 · Cited by 2
“Phenotypic resistance was observed even in early clinical trials [34], most commonly associated with mutations in Rv0678 , a transcriptional repressor of the MmpS5-MmpL5 efflux pump [35].”
Circumnavigating Antibiotic Mechanisms of Action and Resistance Research
Priya, M., & de Carvalho, L. P. S. (2026) · Biochemistry · doi:10.1021/acs.biochem.5c00658 · Cited by 5
A bactericidal tuberculosis drug regimen driven by inhibition of the terminal oxidases by pretomanid
Rahman, N. B. A., Singh, S., Wiggins, T. J., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-026-00378-9 · Cited by 2
“Over the past decade, three drugs have gained approval for clinical use: bedaquiline (Andries et al, 2005) in 2012 (Gras, 2013) was swiftly succeeded by delamanid (Ryan and Lo, 2014) and, more recently, pretomanid (Deb and Biswas, 2021).”
Berlureau, J., Anger, R., Beaulieu, E., Gourgues, G., Bataille, L., Jaubert, J., Lartigue, C., Sirand‐Pugnet, P., & Arfi, Y. (2026) · PLoS Pathogens · doi:10.1371/journal.ppat.1014043 · Cited by 3
Roy, A., Naik, D., Sau, S., Agnivesh, P. K., Parida, K. K., & Kalia, N. P. (2026) · ACS Infectious Diseases · doi:10.1021/acsinfecdis.5c01066 · Cited by 3
Gao, J., Huang, Z., Ren, F., et al. (2026) · Infection · doi:10.1007/s15010-026-02734-w · Cited by 2
Self-citationArbex, M. A. (2026) · Microorganisms · doi:10.3390/microorganisms14051015 · Cited by 2
“Structurally, BDQ is the first in its class and presents a quilinolic central heterocyclic nucleus, with alcohol and amine side chains responsible for its antimycobacterial activity [111–113 , 117 ].”
Bedaquiline inhibits the ATP synthase leak channel and prevents glutamate-induced neuronal death
Kumar, A. P., Lunko, O., Smith, E., Mezghani, I., Eedarapalli, S., Wu, Y., Ferdous, K. A., Amjad, E., Park, H.-A., & Mnatsakanyan, N. (2026) · Biophysical Reports · doi:10.1016/j.bpr.2026.100265 · Cited by 2
“52,53 BDQ was reported to bind at the interface of the c-ring and the a-subunit of mammalian 39 and M . tuberculosis 39,54 ATP synthase in cryo-EM structures.”
Microbial Whole-Genome Sequencing: Applications in Clinical Microbiology and Public Health
(2016) · Molecular Microbiology · doi:10.1128/9781555819071.ch3 · Cited by 2
Access to experimental medicines for TB: ethical and human rights considerations
Dagron, S., Chakhaia, T., González-Angulo, L., et al. (2020) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.18.0885 · Cited by 2
Lugovkina, T. K., Skornyakov, S., Kildyusheva, E., et al. (2020) · Tuberculosis and lung diseases · doi:10.21292/2075-1230-2020-98-6-60-69 · Cited by 2
Dutta, E., DeJesus, M. A., Ruecker, N., Zaveri, A., Koh, E., Sassetti, C. M., Schnappinger, D., & Ioerger, T. R. (2021) · PLoS ONE · doi:10.1371/journal.pone.0257911 · Cited by 2
“Specifically, BDQ binds to subunit C of the membrane complex [25] (which is annotated as atpE in the Mtb genome).”
BackgroundAddressing bedaquiline treatment interruptions in the treatment of drug-resistant TB
Kambili, C., Rossenu, S., Hoetelmans, R. M. W., Birmingham, E., & Bakare, N. (2022) · The International Journal of Tuberculosis and Lung Disease · doi:10.5588/ijtld.21.0678 · Cited by 2
Pérez-Martínez, D. E., Mejía‐Ponce, P. M., Licona‐Cassani, C., de Igartua, E., Bermúdez, G., Viveros, D., & Zenteno‐Cuevas, R. (2023) · Integrated science · doi:10.1007/978-3-031-15955-8_18 · Cited by 2
New Alternatives in the Fight against Tuberculosis: Possible Targets for Resistant Mycobacteria
Rodríguez-Bustamante, E., Gómez‐Manzo, S., del Valle, A. D. O. F., Arreguín‐Espinosa, R., Espitia-Pinzón, C., & Rodríguez-Flores, E. (2023) · Processes · doi:10.3390/pr11092793 · Cited by 2
Yang, W., Tian, Z.-Y., Lin, Y.-J., et al. (2024) · Molecules · doi:10.3390/molecules29122863 · Cited by 2
“Quinolines are an important class of heterocyclic compounds that are widely present in natural products, medicine, functional materials and other fields [1–6].”
BackgroundRecent Biochemical Advances in Antitubercular Drugs: Challenges and Future
Jain, A., Kumar, R., Mothsra, P., Sharma, A., Singh, A. K., & Kumar, Y. (2024) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266286294240610102911 · Cited by 3
Discovery and development of new antibacterial drugs
Elassal, E. S., Fahmy, A., Saad, A. N. M., Ali, A. H., Elshenety, A. H., Badr, O. A., Amer, A. N., Fouda, W. M., & Elshaier, Y. A. M. M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18866-4.00012-2 · Cited by 2
New bedaquiline salt with improved bioavailability and reduced food effect
Zhang, X., Meng, D., Zang, Z., et al. (2024) · CrystEngComm · doi:10.1039/d4ce00567h · Cited by 2
Host-Directed Omics Approaches to Tackle Antimicrobial Resistance
Rastogi, S., & Chandra, P. (2024) · Springer eBooks · doi:10.1007/978-3-031-65986-7_10 · Cited by 2
Chen, S., Shang, Y., Zheng, J., Huo, F., Xue, Y., Zhao, L., Jiang, G., Chu, N., & Huang, H. (2024) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkae405 · Cited by 3
Goel, R., Tomar, A., & Bawari, S. (2024) · Microbial Pathogenesis · doi:10.1016/j.micpath.2024.107116 · Cited by 2
Mice infected with M . tuberculosis with Rv0678 mutations still benefit from bedaquiline treatment
Lounis, N., Gevers, T., Villellas, C., et al. (2024) · IJTLD OPEN · doi:10.5588/ijtldopen.23.0527 · Cited by 2
Self-citationInhibitors of NADH–O-methylquinone compound a class of antitubercular drugs
Lin, D., Xu, C. Y., Gan, C., et al. (2025) · Molecular Diversity · doi:10.1007/s11030-025-11117-6 · Cited by 2
Bundutidi, G. M., Mochizuki, K., Matsuo, Y., Hayashishita, M., Sakura, T., Ando, Y., Cook, G. M., Acharjee, R., Bringaud, F., Boshart, M., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-07611-0 · Cited by 2
Ward, K. T., Williams, A. P. L., Dennison, A. L., Aamir, L., Allen, D. L., Chavez-Arellano, B., Marchlewski, T. A., Zappia, M. L., Wolfe, A. L., & Steed, R. (2025) · ChemMedChem · doi:10.1002/cmdc.202400952 · Cited by 2
The mutant selection window of moxifloxacin and bedaquiline resistant Mycobacterium tuberculosis
Sonnenkalb, L., Trubenová, B., Regoes, R. R., Merker, M., & Niemann, S. (2025) · Journal of Infection · doi:10.1016/j.jinf.2025.106523 · Cited by 3
Kavanagh, M. E., McLean, K. J., Gilbert, S. H., Amadi, C. N., Snee, M., Tunnicliffe, R. B., Arora, K., Boshoff, H. I., Fanourakis, A., Rebollo-López, M. J., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00478 · Cited by 4
“10,11 Numerous studies have also demonstrated that the ability of bedaquiline to modulate Mtb metabolism helps counteract drug resistance mechanisms, 12 synergizes with existing drugs, 13 and may enhance the antibacterial activity of host macrophages.”
Computational Insight into the Binding Mechanism of Pyrazinoic Acid to RpsA Protein
Rehman, A. U., Ali, S., Rafiq, H., et al. (2021) · Current Chinese Science · doi:10.2174/2210298101666210108105814 · Cited by 2
Quinoxalinas como potenciales agentes Antimycobacterium tuberculosis: una revisión
Santivañez‐Veliz, M., Moreno‐Viguri, E., Monge, A., et al. (2013) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 2
A Importância do Núcleo Quinolínico e seus Derivados no Desenvolvimento de Fármacos.
Pinheiro, A. C., Bispo, M. L. F., & Souza, M. V. N. D. (2010) · Revista Fitos · doi:10.32712/2446-4775.2010.119 · Cited by 2
Conformational isomerization of N-(naphthalen-1-yl)-N-(phenyl(quinolin-3-yl)methyl)amide derivatives
Cai, Z., Zhu, C., Cui, Y., et al. (2009) · Science China Chemistry · doi:10.1007/s11426-009-0181-1 · Cited by 2
Khedkar, S. A., Malde, A. K., & Coutinho, E. C. (2007) · Journal of Molecular Modeling · doi:10.1007/s00894-007-0234-3 · Cited by 2
Tuberculosis and its future management
Moore-Gillon, J. C. (2007) · Thorax · doi:10.1136/thx.2007.090936 · Cited by 2
Strategies to Improve Outcome of Drug Treatment for Mycobacterium abscessus Pulmonary Disease
van Ingen, J. (2011) · Clinical Infectious Diseases · doi:10.1093/cid/cir148 · Cited by 2
The future for lung disease in children
Lenney, W. (2007) · Thorax · doi:10.1136/thx.2007.090969 · Cited by 2
Challenges and Opportunities in Tuberculosis Drug Discovery: An Industry Perspective
Shirude, P. S., Ramachandran, S. A., & Hosagrahara, V. P. (2013) · Future Medicinal Chemistry · doi:10.4155/fmc.13.26 · Cited by 2
CAMBer: An approach to support comparative analysis of multiple bacterial strains
Woźniak, M., Wong, L., & Tiuryn, J. (2010) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm.2010.5706549 · Cited by 2
A nucleophilic 1,3-rearrangement leading to 3,4-disubstituted 3,4-dihydroquinolines
He, C., Jiang, Z., Cui, H., et al. (2016) · Chinese Chemical Letters · doi:10.1016/j.cclet.2016.02.030 · Cited by 2
The Medicinal Chemistry of Novel Molecules in Clinical Trials for Tuberculosis Treatment
Branco, F. S. C., Pinto, A. C., & Boechat, N. (2012) · Revista Virtual de Química · doi:10.5935/1984-6835.20120023 · Cited by 2
New drug candidates in tuberculosis treatment
Aksöz, B. E. (2014) · Turkish Bulletin of Hygiene and Experimental Biology · doi:10.5505/turkhijyen.2014.35492 · Cited by 2
“Farelerde bedaquiline oral yolla alındığında uygun bir doku dağılımı ve uzun bir yarı ömür göstermektedir (48).”
BackgroundPharmacokinetics and Pharmacodynamics of the Tuberculosis Drugs
Barth, A., Egelund, E. F., & Peloquin, C. A. (2016) · Methods in pharmacology and toxicology · doi:10.1007/978-1-4939-3323-5_16 · Cited by 2
Hit and Lead Generation Strategies
Ettmayer, P., Schnitzer, R., Bergner, A., & Nar, H. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.12313-3 · Cited by 2
Strategies for Tackling Drug Resistance in Tuberculosis
Maveyraud, L. (2017) · Springer eBooks · doi:10.1007/978-981-10-5187-6_7 · Cited by 2
Li, L., Jin, Y., Wang, B., Yang, Z., Liu, M., Guo, H., Zhang, J., & Lu, Y. (2017) · Chemical Biology & Drug Design · doi:10.1111/cbdd.13142 · Cited by 2
Drug Resistance in Tuberculosis
Schluger, N. W. (2018) · Springer eBooks · doi:10.1007/978-3-319-78538-7_5 · Cited by 2
Host–Pathogen Interactions Influencing Mycobacterium tuberculosis Persistence and Drug Tolerance
Zheng, H., & Abramovitch, R. B. (2019) · Springer eBooks · doi:10.1007/978-3-030-25241-0_10 · Cited by 2
Repurposing of Carbapenems for the Treatment of Drug-Resistant Tuberculosis
Kumar, P., Singh, U. B., Lamichhane, G., et al. (2019) · Springer eBooks · doi:10.1007/978-981-32-9413-4_26 · Cited by 2
Vatlin, A. A., & Даниленко, В. Н. (2020) · Biology Bulletin Reviews · doi:10.1134/s2079086420060067 · Cited by 2
Gao, J., Xie, L., Ma, L., et al. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i10.2326 · Cited by 2
Akbal, A. U., Çoban, A. Y., & Durupınar, B. (2018) · Türk Mikrobiyoloji Cemiyeti Dergisi · doi:10.5222/tmcd.2018.087 · Cited by 2
Drugs used in tuberculosis and leprosy
Swaminathan, S., & Rekha, V. V. B. (2009) · Side effects of drugs annual · doi:10.1016/s0378-6080(09)03130-4 · Cited by 2
Energy Pathways in Mycobacterium Tuberculosis
Ganeshpurkar, A., Singh, R. P., Singh, M., Kumar, A., & Singh, S. K. (2023) · Integrated science · doi:10.1007/978-3-031-15955-8_25 · Cited by 2
Antimicrobial applications of MXenes
Seele, P. P., & Mlambo, M. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13589-7.00009-2 · Cited by 3
Makarova, M. V., Mikhailova, Y. D., Khachaturiants, E., & Litvinov, V. I. (2022) · Tuberkulez i socialʹno značimye zabolevaniâ · doi:10.54921/2413-0346-2022-10-4-47-94 · Cited by 2
(1R*,2R*)-1-(4-Chlorophenyl)-4-dimethylamino-1-(3-methoxy-2-naphthyl)-2-(1-naphthyl)butan-2-ol
Liu, P., Xiao, J., Zhong, W., et al. (2010) · Acta Crystallographica Section E Structure Reports Online · doi:10.1107/s160053681001891x · Cited by 2
“Comment The compound (1R,2S)-1-(6-bromo-2-methoxyquinolin-3-yl)-4-(dimethylamino)-2-(naphthalene- 1-yl)-1-phenylbutan-2ol, is a promising drug against tuberculosis (Andries et al., 2005; Cohen, 2004 and Guillemont et al. 2004).”
BackgroundBédaquiline : de l’in vitro aux essais cliniques d’un nouvel antituberculeux
Guglielmetti, L., & Robert, J. (2015) · Journal des Anti-infectieux · doi:10.1016/j.antinf.2014.12.003 · Cited by 2
High Throughput Genotyping for Genomic Cohort Study
Park, W. (2007) · Journal of Preventive Medicine and Public Health · doi:10.3961/jpmph.2007.40.2.102 · Cited by 2
“1Mb 123ض Mycobacterium tuberculosis 2005z SciencegUÙ ̄ [4].”
Treatment options for MDR- and XDR-TB
Chang, K. C., & Sotgiu, G. (2017) · European Respiratory Society eBooks · doi:10.1183/2312508x.10005616 · Cited by 2
Tang, B., Wei, M., Niu, Q., et al. (2017) · BioMed Research International · doi:10.1155/2017/5791781 · Cited by 2
Domalain, V., Hubert‐Roux, M., Quéguiner, L., et al. (2018) · European Journal of Mass Spectrometry · doi:10.1177/1469066718813226 · Cited by 2
“It is estimated that one-third of the world population is latently infected with TB bacilli.1 Diarylquinolines is a new structural class of antimycobacterials in which SirturoTM (Bedaquiline, Figure 1) is the leader being highly effective against both Mycobacterium tuberculosis and multidrug-resistant TB.2 As the mole…”
BackgroundMethodInfluentialSelf-citationChallenges and Advances in TB Drug Discovery
Khare, G., Nangpal, P., & Tyagi, A. K. (2019) · Springer eBooks · doi:10.1007/978-981-32-9413-4_25 · Cited by 2
Physiological roles of the three [NiFe]-hydrogenases in Mycobacterium smegmatis
Greening, C. A. (2013) · Otago University Research Archive (University of Otago) · doi:10.13140/2.1.1381.1841 · Cited by 3
Campen, R. (2015) · Open Access Victoria University of Wellington | Te Herenga Waka (Figshare) · doi:10.26686/wgtn.17009687.v1 · Cited by 3
“Bedaquiline is a diarylquinoline, the first novel class of anti-mycobacterials to be discovered in 40 years (Andries et al., 2005).”
BackgroundDeveloping Infectious Disease Strategies for the Developing World
Lee, J. S., & Krilov, L. R. (2006) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(06)41018-6 · Cited by 2
A Trial Involving HIV-Tuberculosis in India: The Minute Particulars
Vernon, A. (2010) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200912-1822ed · Cited by 2
“Some of the new anti-TB agents under development offer promise of intermittency due to their long half-lives (16), but these agents will not soon be available for programmatic use in drug-susceptible TB.”
BackgroundDevelopment of new antituberculosis drugs: Its relevance worldwide and in the Asia–Pacific region
Tam, C. M. (2008) · Respirology · doi:10.1111/j.1440-1843.2008.01342.x · Cited by 2
New Agents for the Treatment of Tuberculosis on Clinical Study Phases II/III
Conde, M. B., & Villarino, M. E. (2007) · Current Respiratory Medicine Reviews · doi:10.2174/157339807780599144 · Cited by 2
Metadata
- Authors
- Andries, K., Verhasselt, P., Guillemont, J., Göhlmann, H. W. H., Neefs, J.-M., Winkler, H., Van Gestel, J., Timmerman, P., Zhu, M., Lee, E., Williams, P., de Chaffoy, D., Huitric, E., Hoffner, S., Cambau, E., Truffot-Pernot, C., Lounis, N., & Jarlier, V.
- Affiliations
- Johnson & Johnson (United Kingdom) (GB)
- Johnson & Johnson Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
- Corresponding author
- Andries, Koen
- Lounis, Nacer
- Venue
- Science
- Published
- 2005-01-14
- Volume
- 307
- Issue
- 5707
- Pages
- 223-227
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2158658436
- Cited by
- 2,191
- References
- 13
- Citations by year
- 2026: 63 · 2025: 98 · 2024: 103 · 2023: 106 · 2022: 111 · 2021: 98 · 2020: 136 · 2019: 141 · 2018: 102 · 2017: 124 · 2016: 120 · 2015: 129 · 2014: 140 · 2013: 106 · 2012: 102
- FWCI
- 27.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Keywords
- diarylquinolines, Mycobacterium tuberculosis, tuberculosis drug resistance, ATP synthase inhibition, proton pump, bactericidal activity, combination therapy, isoniazid
- MeSH terms
- Amino Acid Sequence, Animals, Antitubercular Agents, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Drug Therapy, Combination
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