Design, Synthesis, and Antifungal Activity of Thiazolidinedione Derivatives Incorporating Thioamide and Piperidine Moieties

Abstract

A series of thiazolidinedione derivatives containing thioamide and piperidine moieties were designed, synthesized, and evaluated for antifungal activity against plant pathogenic fungi. Several compounds exhibited potent antifungal activity, among which Z17 was the most active against Rhizoctonia solani (EC50 = 1.8 μg/mL), with substantially greater activity than azoxystrobin (Az; EC50 = 42.6 μg/mL). Physiological analyses indicated that Z17 disrupted membrane integrity and cellular energy metabolism, as reflected by increased malondialdehyde levels and decreased pyruvate kinase activity and pyruvate content. Density functional theory calculations, molecular docking, and molecular dynamics simulations suggested that Z17 forms favorable interactions with the cytochrome bc1 complex. Preliminary safety assessments showed no significant effects on rice seed germination or earthworm viability. These findings suggest Z17 as a promising lead for the development of antifungal agents against crop pathogens.