Expedient discovery for novel antifungal leads: 1, 3, 4-Oxadiazole derivatives bearing a quinazolin-4(3H)-one fragment. (1st September 2021)

• Record Type: Journal Article
• Authors: Wang, Xiaobin; Chai, Jianqi; Kong, Xiangyi; Jin, Fei; Chen, Min; Yang, Chunlong; Xue, Wei
• Is Part Of: Bioorganic & medicinal chemistry. Volume 45(2021)
• Publication Date: 2021-09-01
• Subjects: Quinazolin-4(3H)-one -- 1, 3, 4-Oxadiazole -- Lead discovery -- Antifungal activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2021.116330
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Developing novel fungicide candidates are intensively promoted by the rapid emergences of resistant fungi that outbreak on agricultural production. Aiming to discovery novel antifungal leads, a series of 1, 3, 4-oxadiazole derivatives bearing a quinazolin-4(3 H )-one fragment were constructed for evaluating their inhibition effects against phytopathogenic fungi in vitro and in vivo . Systematically structural optimizations generated the bioactive molecule I32 that was identified as a promising inhibitor against Rhizoctonia solani with the in vivo preventative effect of 58.63% at 200 μg/mL. The observations that were captured by scanning electron microscopy and transmission electron microscopy demonstrated that the bioactive molecule I32 could induce the sprawling growth of hyphae, the local shrinkage and rupture on hyphal surfaces, the extreme swelling of vacuoles, the striking distortions on cell walls, and the reduction of mitochondria numbers. The above results provided an indispensable complement for the discovery of antifungal lead bearing a quinazolin-4(3 H )-one and 1, 3, 4-oxadiazole fragment.