%0 Journal Article
%T Degradation-Risk-Inspired Optimization of the Antifungal Oxazolinyl Aniline Lead by a Fusion of Triazole with Nicotinamide.
%A Li M
%A Kong W
%A Sun S
%A He X
%A Li S
%J J Agric Food Chem
%V 72
%N 31
%D 2024 Aug 7
%M 39046270
%F 5.895
%R 10.1021/acs.jafc.4c02025
%X The discovery of readily available and easily modifiable new models is a crucial and practical solution for agrochemical innovation. Antifungal function-oriented fusion of triazole with the prevalidated lead (R)-LE001 affords a novel framework with a broad and enhanced antifungal spectrum. Characterized by the easy accessibility and adjustability of [1,2,4]triazolo[4,3-a]pyridine, modular fine-tuning provided a set of unprecedented leads (e.g., Z23, Z25, Z26, etc.) with superior antifungal potentials than the positive control boscalid. Candidate Z23 exhibited a more promising antifungal activity against Sclerotinia sclerotiorum, Botrytis cinerea, and Phytophthora capsici with EC50 values of 0.7, 0.6, and 0.5 μM, respectively. This candidate could effectively control boscalid-resistant B. cinerea strains and also exhibit good vivo efficacy in controlling gray mold. Noteworthily, both the SDH-inhibition and the efficiency against Oomycete P. capsici are quite distinct from that of the positive control boscalid. A molecular docking simulation also differentiates Z23 from boscalid. These findings highlight the potential of [1,2,4]triazolo[4,3-a]pyridine amide as a novel antifungal model.