Nikkomycin

Nikkomycins are a group of antifungal medications.[1] They work by interfering with the building of the fungal cell wall which results in the fungal cell breaking open.[1] They were discovered in 1976.[1] The nikkomycins were discovered to be highly active against the dimorphic fungi Coccidioides immitis, Blastomyces dermatitidis, and Histoplasma capsulatum, with nikkomycin Z more active than nikkomycin X both in vitro and in vivo in mouse models[2]. Nikkomycin Z was also found to interact synergistically with multiple azole antifungals against Candida albicans, both in vitro and in vivo in mouse models[3]. The specific agent nikkomycin Z has weak activity against Aspergillus fumigatus which may be of benefit when used with other medications,[1] such as caspofungin, ranconazole and amphotericin B, fluconazole or itraconazole.[4] Nikkomycin Z also inhibits growth of Batrachochytrium dendrobatidis, a serious fungal pathogen linked to global amphibian declines, while lower concentrations of Nikkomycin Z enhanced natural amphibian antimicrobial skin peptide effectiveness in vitro.[5] The safety and pharmacokinetics of single doses of nikkomycin Z was evaluated in a Phase I study in humans[6].

Originally identified from Streptomyces tendae, the nikkomycins are chitin synthase inhibitors.[4]

References

  1. ^ a b c d Steinbach, WJ; Stevens, DA (1 October 2003). "Review of newer antifungal and immunomodulatory strategies for invasive aspergillosis". Clinical Infectious Diseases. 37 (Suppl 3): S157-87. doi:10.1086/376523. PMID 12975751.
  2. ^ Hector, R. F.; Zimmer, B. L.; Pappagianis, D. (1990-04). "Evaluation of nikkomycins X and Z in murine models of coccidioidomycosis, histoplasmosis, and blastomycosis". Antimicrobial Agents and Chemotherapy. 34 (4): 587–593. doi:10.1128/AAC.34.4.587. ISSN 0066-4804. PMC 171648. PMID 2344165. {{cite journal}}: Check date values in: |date= (help)
  3. ^ Hector, R. F.; Schaller, K. (1992-06). "Positive interaction of nikkomycins and azoles against Candida albicans in vitro and in vivo". Antimicrobial Agents and Chemotherapy. 36 (6): 1284–1289. doi:10.1128/AAC.36.6.1284. ISSN 0066-4804. PMC 190333. PMID 1416829. {{cite journal}}: Check date values in: |date= (help)
  4. ^ a b Varnava, Kyriakos G.; Ronimus, Ron S.; Sarojini, Vijayalekshmi (November 2017). "A review on comparative mechanistic studies of antimicrobial peptides against archaea". Biotechnology and Bioengineering. 114 (11): 2457–2473. doi:10.1002/bit.26387. PMID 28734066. S2CID 25183554.
  5. ^ Holden, Whitney M; Fites, J Scott; Reinert, Laura K; Rollins-Smith, Louise A (January 2014). "Nikkomycin Z is an effective inhibitor of the chytrid fungus linked to global amphibian declines". Fungal Biology. 118 (1): 48–60. doi:10.1016/j.funbio.2013.11.001. PMID 24433676.
  6. ^ Nix, David E.; Swezey, Robert R.; Hector, Richard; Galgiani, John N. (2009-06). "Pharmacokinetics of nikkomycin Z after single rising oral doses". Antimicrobial Agents and Chemotherapy. 53 (6): 2517–2521. doi:10.1128/AAC.01609-08. ISSN 1098-6596. PMC 2687243. PMID 19349517. {{cite journal}}: Check date values in: |date= (help)
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