Natural products as a robust source of new drugs and drug leads: Past successes and present day issues
Abstract
The history of drug development has its foundation firmly set in the study of natural remedies used to treat human disease over centuries. Analysis of medicinal plants, bioactive cultures, and increased understanding of micronutrients in the food chain opened the door to the development of purified and defined chemical compounds as dose-controlled medicines. Thus, with the early discovery of cardiotonics in foxglove, salicylic acid in willow bark, morphine in poppies, and penicillin in mold, the pharmaceutical industry was launched. Such natural small molecules served as treatments for disease and ultimately, as pharmacologic tools to enable the understanding of the biochemical pathways and mechanisms of disease. In contrast, modern drug discovery technologies coupled with the powerful tools of biotechnology have prompted drug discovery organizations to focus on target-driven drug discovery at the molecular level by launching high-throughput screening programs using artificial biochemical assays. At a time when the pharmaceutical industry has come under scrutiny for high rates of drug development failure, it is interesting to see that natural products drug discovery has been marginalized in favor of this high-throughput biochemical screening paradigm. If modern drug development is once again to benefit from natural products as a source, then the limitations of artificial biochemical assays as applied to the screening of natural extracts must be realized in order to capitalize on the vast natural molecular diversity and rich ethnobotanic data that has emerged worldwide. Natural compounds can again become central players in the treatment of disease and in the understanding of disease mechanisms.
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Allicin is a lipid-soluble sulfur compound that can be easily damaged by cooking and can provoke intolerance, allergic reactions, and gastrointestinal disorders.
“Allicin is a lipid-soluble sulfur compound, which can be easily damaged by cooking and has the ability to provoke intolerance, allergic reactions, and gastrointestinal disorders [27,28,29].”
From Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review (2020) · cites this paper as [27]
Cites
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139 · see citing works
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,484 · see citing works
Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-like Drugs
VANE, J. R. (1971) · Nature New Biology · doi:10.1038/newbio231232a0 · Cited by 8,605 · see citing works
Natural products as sources of new drugs over the last 25 years
Newman, D. J., & Cragg, G. M. (2007) · Journal of Natural Products · doi:10.1021/np068054v · Cited by 5,517 · see citing works
A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening
McGovern, S. L., Caselli, E., Grigorieff, N., & Shoichet, B. K. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm010533y · Cited by 1,048 · see citing works
Navigating chemical space for biology and medicine
Lipinski, C. A., & Hopkins, A. L. (2004) · Nature · doi:10.1038/nature03193 · Cited by 1,008 · see citing works
Astaxanthin, a Carotenoid with Potential in Human Health and Nutrition
Hussein, G. M. E., Sankawa, U., Goto, H., Matsumoto, K., & Watanabe, H. (2005) · Journal of Natural Products · doi:10.1021/np050354+ · Cited by 653 · see citing works
Natural products and drug discovery
Ji, H., Li, X., & Zhang, H. (2009) · EMBO Reports · doi:10.1038/embor.2009.12 · Cited by 648 · see citing works
The Renaissance of Natural Products as Drug Candidates
Paterson, I., & Anderson, E. A. (2005) · Science · doi:10.1126/science.1116364 · Cited by 559 · see citing works
Small Molecule Natural Products in the Discovery of Therapeutic Agents: The Synthesis Connection
Wilson, R. M., & Danishefsky, S. J. (2006) · The Journal of Organic Chemistry · doi:10.1021/jo0610053 · Cited by 387 · see citing works
Nonleadlikeness and leadlikeness in biochemical screening
Rishton, G. M. (2003) · Drug Discovery Today · doi:10.1016/s1359644602025722 · Cited by 381 · see citing works
Self-citationReactive compounds and in vitro false positives in HTS
Rishton, G. M. (1997) · Drug Discovery Today · doi:10.1016/s1359-6446(97)01083-0 · Cited by 348 · see citing works
Self-citationAstaxanthin and canthaxanthin are potent antioxidants in a membrane model
Palozza, P., & Krinsky, N. I. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90675-m · Cited by 346 · see citing works
Skou, J. C. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)56004-4 · Cited by 303 · see citing works
McNulty, H. P., Byun, J., Lockwood, S. F., Jacob, R. F., & Mason, R. P. (2006) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2006.09.010 · Cited by 270 · see citing works
Zhang, L., & Demain, A. L. (2005) · Humana Press eBooks · doi:10.1007/978-1-59259-976-9 · Cited by 208 · see citing works
Alexander Fleming and the discovery of penicillin
Bennett, J. W., & Chung, K.-T. (2001) · Advances in applied microbiology · doi:10.1016/s0065-2164(01)49013-7 · Cited by 201 · see citing works
Natural Products and Drug Discovery
Demain, A. L., & Zhang, L. (2007) · Humana Press eBooks · doi:10.1007/978-1-59259-976-9_1 · Cited by 153 · see citing works
Gaudillière, J. (2005) · Studies in History and Philosophy of Science Part C Studies in History and Philosophy of Biological and Biomedical Sciences · doi:10.1016/j.shpsc.2005.09.006 · Cited by 149 · see citing works
Developments in world aquaculture, feed formulations and role of carotenoids
Meyers, S. P. (1994) · Pure and Applied Chemistry · doi:10.1351/pac199466051069 · Cited by 121 · see citing works
Improvement of Biochemical Features in Fish Health by Red Yeast and Synthetic Astaxanthin
Nakano, T., Tosa, M., & Takeuchi, M. (1995) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf00054a029 · Cited by 115 · see citing works
The Quantity And Quality Of Worldwide New Drug Introductions, 1982–2003
Grabowski, H. G., & Wang, Y. R. (2006) · Health Affairs · doi:10.1377/hlthaff.25.2.452 · Cited by 103 · see citing works
An Account of the Foxglove and Its Medical Uses 1785-1985
Aronson, J. K. (1986) · Cited by 83 · see citing works
Cyclooxygenase-2 Inhibitors: A Painful Lesson
Sanghi, S., MacLaughlin, E. J., Jewell, C. W., Chaffer, S., Naus, P., Watson, L. E., & Dostal, D. E. (2006) · Cardiovascular & Haematological Disorders - Drug Targets · doi:10.2174/187152906777441803 · Cited by 73 · see citing works
Tissue distribution of astaxanthin in rats following exposure to graded levels in the feed
Petri, D., & Lundebye, A. (2006) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2006.12.008 · Cited by 73 · see citing works
Selective inhibitors of cyclooxygenase-2: a growing class of anti-inflammatory drugs.
Ia, M., & FitzGerald, G. A. (2001) · PubMed · Cited by 63 · see citing works
High Throughput Screening for Drug Discovery: Continually Transitioning into New Technology
Fox, S., Farr-Jones, S., & Yund, M. A. (1999) · SLAS DISCOVERY · doi:10.1177/108705719900400405 · Cited by 60 · see citing works
Ghuysen, J. (1997) · International Journal of Antimicrobial Agents · doi:10.1016/s0924-8579(96)00358-5 · Cited by 59 · see citing works
LXXII.—Digoxin, a new digitalis glucoside
Smith, S. (1930) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9300000508 · Cited by 45 · see citing works
Burnier, M. (2005) · Expert Opinion on Drug Safety · doi:10.1517/14740338.4.3.491 · Cited by 38 · see citing works
Fisch, C. (1985) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(85)80456-3 · Cited by 34 · see citing works
Prelude to the Discovery of Penicillin
Landsberg, H. (1949) · Isis · doi:10.1086/349043 · Cited by 32 · see citing works
Ghuysen, J. (2002) · Encyclopedia of Molecular Biology · doi:10.1002/047120918x.emb1092 · Cited by 31 · see citing works
Sashidhara, K. V., & Rosaiah, J. N. (2007) · Natural Product Communications · doi:10.1177/1934578x0700200218 · Cited by 30 · see citing works
Ignelzi, R. J., & Atkinson, H. J. (1980) · Neurosurgery · doi:10.1227/00006123-198005000-00016 · Cited by 21 · see citing works
Ramírez, P., Santoyo, S., García‐Risco, M. R., et al. (2007) · Journal of Chromatography A · doi:10.1016/j.chroma.2006.12.096 · Cited by 21 · see citing works
Smyth, W. F., McClean, S., Hack, C. J., et al. (2006) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2006.04.003 · Cited by 17 · see citing works
Hydrophilic Carotenoid Amphiphiles: Methods of Synthesis and Biological Applications
Foss, B. J., Nadolski, G., & Lockwood, S. F. (2006) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955706778195225 · Cited by 16 · see citing works
Mueller-Kuhrt, L. (2007) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2.3.305 · Cited by 11 · see citing works
Digoxin, a new digitalis glucoside
Smith, S. (1930) · Cited by 10 · see citing works
A hierarchical screening methodology for physicochemical/ADME/Tox profiling
DeWitte, R. S., & Robins, R. H. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.5.805 · Cited by 8 · see citing works
[Sertürner and the discovery of morphine].
Lassner, J. (1993) · PubMed · Cited by 7 · see citing works
Anilines: Historical Background
Travis, A. S. (2009) · Patai's chemistry of functional groups · doi:10.1002/9780470682531.pat0383 · Cited by 5 · see citing works
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Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.): A Review
El-Saber Batiha, G., Magdy Beshbishy, A., G. Wasef, L., Elewa, Y. H. A., A. Al-Sagan, A., Abd El-Hack, M. E., Taha, A. E., M. Abd-Elhakim, Y., & Prasad Devkota, H. (2020) · Nutrients · doi:10.3390/nu12030872 · Cited by 931 · see citing works
Allicin: Chemistry and biological properties
Borlinghaus, J., Albrecht, F., Gruhlke, M., Nwachukwu, I., & Slusarenko, A. (2014) · Molecules · doi:10.3390/molecules190812591 · Cited by 893 · see citing works
Kurita, K. L., Glassey, E., & Linington, R. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1507743112 · Cited by 156 · see citing works
- Authors
- Rishton, G. M.
- Affiliations
- California State University, Channel Islands (US)
- Corresponding author
- Rishton, Gilbert M.
- Venue
- The American Journal of Cardiology
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 101
- Issue
- 10
- Pages
- S43-S49
- ISSN
- 0002-9149 (ISSN-L)
- OpenAlex
- W2087870568
- Cited by
- 276
- References
- 43
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 12 · 2023: 23 · 2022: 13 · 2021: 13 · 2020: 23 · 2019: 21 · 2018: 13 · 2017: 15 · 2016: 21 · 2015: 14 · 2014: 19 · 2013: 8 · 2012: 19
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioactive natural compounds
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Ethnobotanical and Medicinal Plants Studies
- Keywords
- natural products, drug discovery, drug leads, medicinal plants, ethnobotany, high-throughput screening, natural extracts, history of pharmacology, drug development failure, natural product diversity
- MeSH terms
- Biological Products, Drug Industry, Humans, Plant Extracts, Plants, Medicinal, Drug Design, Ethnobotany, History, 18th Century, History, 19th Century, History, 20th Century
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