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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Letter Article

Discovery of Novel Cytochrome bc1 Complex Inhibitor Based on Natural Product Neopeltolide

Author(s): Tao Chen, Rui Zhang, Yu-Xia Wang, Meng-Qi Gao, Qiong Chen*, Xiao-Lei Zhu* and Guang-Fu Yang

Volume 19, Issue 4, 2022

Published on: 06 October, 2021

Page: [263 - 268] Pages: 6

DOI: 10.2174/1570180818666211006142034

Price: $65

Abstract

Background: Natural products (NPs) are important sources for the design of new drugs and agrochemicals. Neopeltolide, a marine NP, has been identified as a potent Qo-site inhibitor of cytochrome bc1 complex.

Methods: In this study, a series of neopeltolide derivatives was designed and synthesized by the simplification of its 14-membered macrolactone ring with a diphenyl ether fragment. The enzymatic inhibition bioassays and mycelium growth inhibition experiments against a range of fungi were performed to determine their fungicidal activities.

Results: The derivatives have potent activity against the porcine bc1 complex. Compound 8q showed the best activity with an IC50 value of 24.41 nM, which was 8-fold more effective than that of positive control azoxystrobin. Compound 8a exhibited a 100% inhibitory rate against Zymoseptoria tritici and Alternaria solani at a 20 mg/L dose.

Conclusion: Computational results indicated that compounds with suitable physicochemical properties, as well as those forming a hydrogen bond with His161, would have good fungicidal activity. These data could be useful for the design of bc1 complex inhibitors in the future.

Keywords: Neopeltolide, bc1 complex, natural product, inhibitor, fungicidal activity, molecular docking.

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