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Mar. Drugs 2019, 17(2), 102; https://doi.org/10.3390/md17020102

Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A

1
Department of Chemistry, University of California, San Diego, 9500 Gilman Drive MC0358, La Jolla, CA 92093, USA
2
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, 9500 Gilman Drive MC0358, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
This paper is dedicated to the memory of Professor Yuzuru Shimizu (1935–2019).
Received: 21 December 2018 / Revised: 21 January 2019 / Accepted: 31 January 2019 / Published: 7 February 2019
(This article belongs to the Special Issue Advances in Marine Alkaloids)
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Abstract

Bengazoles A–G from the marine sponge Jaspis sp. exhibit potent in vitro antifungal activity against Candida spp. and other pathogenic fungi. The mechanism of action (MOA) of bengazole A was explored in Candida albicans under both liquid culture and surface culture on Mueller-Hinton agar. Pronounced dose-dependent synergistic antifungal activity was observed with bengazole A in the presence of bengamide A, which is also a natural product from Jaspis sp. The MOA of bengazole A was further explored by monitoring the sterol composition of C. albicans in the presence of sub-lethal concentrations of bengazole A. The GCMS of solvent extracts prepared from liquid cultures of C. albicans in the presence of clotrimazole―a clinically approved azole antifungal drug that suppresses ergosterol biosynthesis by the inhibition of 14α-demethylase―showed reduced cellular ergosterol content and increased concentrations of lanosterol and 24-methylenedihydrolanosterol (a shunt metabolite of ergosterol biosynthesis). No change in relative sterol composition was observed when C. albicans was cultured with bengazole A. These results eliminate an azole-like MOA for the bengazoles, and suggest that another as-yet unidentified mechanism is operative. View Full-Text
Keywords: antifungal; alkaloid; synergism; Candida albicans antifungal; alkaloid; synergism; Candida albicans
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Jamison, M.T.; Wang, X.; Cheng, T.; Molinski, T.F. Synergistic Anti-Candida Activity of Bengazole A in the Presence of Bengamide A. Mar. Drugs 2019, 17, 102.

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