Design and synthesis of thiazolyl hydrazide derivatives as potent antifungal agent
Year: 2026
Type: article
Abstract: ABSTRACT: Fungal pathogen caused a persistent threat to global agricultural productivity. The emergence of resistance to existing fungicides underscores the urgent need for novel agents with distinct mechanisms of action. Thiazole and hydrazide derivatives exhibit broad-spectrum and potent antifungal activity, demonstrating significant potential as novel antifungal agents. In this paper, 45 thiazolyl hydrazide derivatives were designed and synthesized as potential succinate dehydrogenase (SDH) inhibitors. These compounds exhibited broad-spectrum antifungal activity against seven pathogens, notably compound A5 and A33 showed the most significant activity against Pythium aphanidermatum and Sclerotinia sclerotiorum, and compound A37 with cyclopropyl and 3-chloro-2-fluorophenyl substituents showed significantly efficacy against Rhizoctonia cerealis (EC₅₀=0.49 mg/L) and Alternaria Nees (EC₅₀=1.81 mg/L), while maintaining a comparable protective effect (88.5%) to that of the reference fungicide Bixafen. The structure-activity relationship has also been analyzed in detail. Preliminary mechanistic studies indicated that A37 disrupts the TCA cycle through inhibiting SDH. Concurrently, the activities of SOD and CAT were reduced, resulting in elevated ROS levels and increased MDA content, which will damage the integrity of fungi cell. Molecular docking and molecular dynamics simulation confirmed the binding affinity of A37 with SDH. The cytotoxicity experiment indicated that the thiazolyl hydrazide derivatives belongs to the low-toxicity compounds. These findings suggest the potential of thiazolyl hydrazide derivatives as promising, eco-friendly candidates for the development of novel antifungal agents.
Source: Pest Management Science
DOI: 10.1002/ps.70918
Institution: Hebei University
Language: English
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7161566535