Virtual Screening-Based Synthesis of 1,3,4-Thiadiazole Derivatives and Their Evaluation for Fungicidal Activity, Ergosterol Inhibition, and Aquatic Toxicity

Rhizoctonia solani is a major soil-borne pathogen that causes severe agricultural damage to maize, rice, soybean, and potato. The increasing resistance of pathogens to conventional fungicides and environmental concerns necessitate the development of new, effective, and eco-friendly antifungal compounds. Guided by a comparative docking study, 5-substituted-1,3,4-thiadiazole-2-thiol derivatives were synthesized, characterized, and evaluated for their antifungal efficacy against R. solani . Several derivatives exhibited strong antifungal activity (EC 50: 3.6 to 196.56 μg/mL), particularly those with halogen-substituted phenyl rings. The compound, 5-((2,4-dichlorophenoxy)methyl)-1,3,4-thiadiazole-2-thiol (A-3), showed the highest activity comparable to the reference fungicide hexaconazole (EC 50 = 2.33 μg/mL). Structure–activity relationship analysis and ergosterol inhibition activity affirmed their potential as effective agricultural fungicides, while ECOSAR model predictions indicated their promise as environmentally safe bioactive compounds for plant disease management.