Potent In Vitro Antifungal Activities of Naturally Occurring Acetylenic Acids
| Autor: | Alice M. Clark, Susan P. Manly, Xing-Cong Li, Shabana I. Khan, M. Khalid Ashfaq, Ameeta K. Agarwal, K. Suresh Babu, Hala N. ElSohly, Melissa R. Jacob |
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| Rok vydání: | 2008 |
| Předmět: |
Antifungal Agents
Rubiaceae Aspergillus flavus Microbial Sensitivity Tests Candida parapsilosis Cell Line Aspergillus fumigatus Microbiology Candida tropicalis Mice Trichophyton Candida krusei Candida albicans medicine Animals Humans Pharmacology (medical) Pharmacology Plants Medicinal Molecular Structure biology Candida glabrata Fungi biology.organism_classification Infectious Diseases Biochemistry Susceptibility Alkynes Undecylenic acid Fatty Acids Unsaturated medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 52:2442-2448 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01297-07 |
| Popis: | Our continuing effort in antifungal natural product discovery has led to the identification of five 6-acetylenic acids with chain lengths from C 16 to C 20 : 6-hexadecynoic acid (compound 1), 6-heptadecynoic acid (compound 2), 6-octadecynoic acid (compound 3), 6-nonadecynoic acid (compound 4), and 6-icosynoic acid (compound 5) from the plant Sommera sabiceoides . Compounds 2 and 5 represent newly isolated fatty acids. The five acetylenic acids were evaluated for their in vitro antifungal activities against Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis, Candida parapsilosis, Cryptococcus neoformans, Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Trichophyton mentagrophytes , and Trichophyton rubrum by comparison with the positive control drugs amphotericin B, fluconazole, ketoconazole, caspofungin, terbinafine, and undecylenic acid. The compounds showed various degrees of antifungal activity against the 21 tested strains. Compound 4 was the most active, in particular against the dermatophytes T. mentagrophytes and T. rubrum and the opportunistic pathogens C. albicans and A. fumigatus , with MICs comparable to several control drugs. Inclusion of two commercially available acetylenic acids, 9-octadecynoic acid (compound 6) and 5,8,11,14-eicosatetraynoic acid (compound 7), in the in vitro antifungal testing further demonstrated that the antifungal activities of the acetylenic acids were associated with their chain lengths and positional triple bonds. In vitro toxicity testing against mammalian cell lines indicated that compounds 1 to 5 were not toxic at concentrations up to 32 μM. Furthermore, compounds 3 and 4 did not produce obvious toxic effects in mice at a dose of 34 μmol/kg of body weight when administered intraperitoneally. Taking into account the low in vitro and in vivo toxicities and significant antifungal potencies, these 6-acetylenic acids may be excellent leads for further preclinical studies. |
| Databáze: | OpenAIRE |
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