Structure based approach for twin-enzyme targeted benzimidazolyl-1,2,4-triazole molecular hybrids as antifungal agents

Agri-vitality of benzim dazoles and 1,2,4-triazoles against ergosterol and beta-Tubulin prompted and "lead hybridization" based novel series of benzimidazolyl-1,2,4-triazoles (1-32) were designed as twin-enzyme targeted inhibitors. In silico computational tools viz. molecular docking, Lipinski parameters, Frontier molecular orbital approach and Toxicity analysis screened three benzimidazoly-1,2,4-triazoles out of 32 designed molecules, which were synthesised by multistep protocol and characterized by spectroscopic techniques. Antimycotic activity against F. verticillioides, D. oryzae, C. lunata and F. fujikuroi indicated deca fold enhanced potency of all the synthesised compounds, than the standard commercial benzimidazole fungicide, carbendazim. Compounds 8 exhibited ED(50 )values lower than triazole fungicide, propiconazole. Remarkably, compound 8 inflicted the most promising activity against all the test fungi with ED50 value ranging from 16 to 21 mu g/ml better than the standard commercial fungicides used (Tilt: 20-25 mu g/ml and Carbendazim:150-230 Kg/ml). Ultra microscopic details revealed compound 8 not only caused aberrant distortions resulting in collapsed hyphae but also efficiently shrunken the spores resulting in reproduction inhibition, as possible cause of fungal growth inhibition. (C) 2020 Published by Elsevier B.V. on behalf of King Saud University.