CoChat
Sign Up
Cited by 189Fungal Infections and StudiesAntifungal resistance and susceptibilityFungal and yeast genetics research

Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis

Open access
Hector, R F, Zimmer, B L, Pappagianis, D·1990·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.34.4.587PMC PMC171648
Open this paper in CoChat — free account

Abstract

Nikkomycins X and Z, competitive inhibitors of fungal chitin synthase, were evaluated as therapeutic agents in vitro and in mouse models of coccidioidomycosis, histoplasmosis, and blastomycosis. In vitro, the nikkomycins were found to be most effective against the highly chitinous, dimorphic fungi Coccidioides immitis and Blastomyces dermatitidis, were less effective against yeasts, and were virtually without effect on the filamentous fungus Aspergillus fumigatus. Additionally, by transmission electron microscopy, nikkomycin Z was highly disruptive to the cell wall and internal structure of the spherule-endospore phase of C. immitis in vitro. In vivo, nikkomycin Z was more effective than nikkomycin X, was also found to be superior on a milligram per milligram basis to the majority of azoles tested in the models of coccidioidomycosis and blastomycosis, and was moderately effective in histoplasmosis. A study of the pharmacokinetics in mice showed that nikkomycin Z was rapidly eliminated after intravenous infusion but that absorption after oral administration was sufficiently slow to allow inhibitory levels to persist for more than 2 h. Results of limited toxicology tests suggest that nikkomycin Z was well tolerated at the dosages employed.

Integrity signals

Registry

Crossref · 10.1128/aac.34.4.587

Cites

29 of 29 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

  • Nikkomycin Z has some in vitro activity against C. parapsilosis, Coccidioides immitis, and Blastomyces dermatitidis, but its usefulness relies on synergism with echinocandins for C. albicans, A. fumigatus, and C. immitis.

    “Nikkomycin Z has some in vitro activity against C. parapsilosis, Coccidioides immitis, and Blastomyces dermatitidis (Hector et al., 1990), but its usefulness relies on the synergism with echinocandins for C. albicans, A. fumigatus, and C. immitis (Chiou et al., 2001; Cheung and Hui, 2017).”

    From Fungal Cell Wall: Emerging Antifungals and Drug Resistance. (2019) · cites this paper as Hector et al., 1990

  • Nikkomycin Z is a first-in-class chitin-synthase inhibitor developed as a targeted approach against endemic fungi, including Coccidioides species.

    “Nikkomycin Z is a first-in-class chitin-synthase inhibitor developed by Valley Fever Solutions as a targeted approach against endemic fungi, including Coccidioides species [101].”

    From Investigational Agents for the Treatment of Resistant Yeasts and Molds (2021) · cites this paper as [101]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Hector, R. F., Zimmer, B. L., & Pappagianis, D.
Affiliations
Cutter Biological, Berkeley, California 94710.
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
1990-04
Volume
34
Issue
4
Pages
587-593
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.34.4.587
PMC
PMC171648
OpenAlex
W2166675124
Cited by
189
References
29
Citations by year
2026: 3 · 2025: 6 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 11 · 2020: 8 · 2019: 8 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 3 · 2014: 4 · 2013: 9 · 2012: 3
FWCI
5.98
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
nikkomycin Z, chitin synthase inhibitors, coccidioidomycosis, histoplasmosis, blastomycosis, Coccidioides immitis, Blastomyces dermatitidis, Aspergillus fumigatus, dimorphic fungi, antifungal agents, pharmacokinetics, toxicity
MeSH terms
Administration, Oral, Aminoglycosides, Animals, Anti-Bacterial Agents, Antifungal Agents, Blastomycosis, Coccidioidomycosis, Female, Fungi, Histoplasmosis, Liver, Microbial Sensitivity Tests, Spleen, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review