Synthesis, Antifungal Evaluation, Toxicity Analysis, And In Silico Rationalization Of Some 3-Aryl-1,2,4-Triazolopyridines Against Seed-Borne Fungal Pathogens Of Rice

1,2,4-Triazolopyridines motif of great pharmacological value is almost unexplored in Agri World. The present work pertains to the synthesis of a series of 1-benzylidene-2-(pyridin-2-yl)hydrazines (2-8) by solid-state synthesis followed by its oxidative cyclization to obtain 3-aryl-1,2,4-triazolopyridines (9-15). Antifungal evaluation studies of starting reactants, intermediates, and final products against economically important seed-borne mycoflora of rice, namely, Fusarium verticillioides, Fusarium fujikuroi, and Sarocladium oryzae revealed that all the tested compounds are better fungi toxic than the standard commercial fungicides used. Interface between pymol and molecular docking suites AutoDock and Vina demonstrated them as 14-alpha demethylase inhibitor rationalized by docking visualization aid indicating two strong hydrogenbonded interactions for high docking score of compound 9 than propiconazole (1H bond). Chemical reactivity indices obtained by ChemDraw ultra 3D simulation tools categorized them as "Non-doxin" like, responsible for non-persistence and less toxic behavior of the compounds. The in silico toxicity analysis and actual cell viability test by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays on mammalian stem cell revealed compound 9 (IC50; 75 mu g/ml) to be much lower toxic than propiconazole (IC50; 41.02 mu g/ml), advocating its further exploration for in vivo antifungal assays.