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Published on: February 14, 2018
Core Emulating Optimization of Mycoleptodiscin A for Synthetically Tractable Antifungal Leads
Nvdan Hu1,2, Shengxin Sun1, Xian Ming1
1State Key Laboratory of Green Pesticide, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.
Abstract:
Antifungal function-oriented optimization of mycoleptodiscin A was conceived through synthetically feasible core-emulating optimization. A library of structurally distinct heterocycles with 7 kinds of drimane skeletons and promising antifungal potentials was acquired. Novel mimics 3j, 3k, 7a, 7d, and 8g were obtained as antifungal leads against R. solani. The antifungal spectrum of 3e was different from that of boscalid against P. capsici (EC50 = 13.22 μM vs EC50 > 150 μM) and S. sclerotiorum (EC50 = 7.97 μM vs EC50 = 0.56 μM). Compared with the positive control boscalid (86%), both drimanyl oxazoline 3e and its hydrolyzate (9a) possess good preventative efficacy (73%) at 100 μM against S. sclerotiorum on lettuce leaves. They could effectively inhibit oxalic acid production, damage the cell membrane, and cause mycelium deformation. The less complex drimane heterocycles can serve as promising and accessible models for the discovery of novel antifungal ingredients.
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