Elucidating the biological activities of thiadazole derivatives against Vibrio cholerae: Insights from DFT, spectroscopic studies, molecular docking and ADMET

Abstract

Cholera has become one of the major global health challenges, especially in sub-Saharan Africa, where there is poor hygiene and sanitation, and due to the emergence of a resistant strain of the causative agent of cholera, there is a need for new therapeutic agents. Thiadiazoles are organic compounds that have been reported to have various biological applications. This study comprehensively analysed the structural, electronic, and biological properties of N1,N10-bis(5-(2-oxo-2H-chromen-3yl)-1,3,4-thiadiazol-2-yl)-decane-diamide, a thiadiazole derivative (TDZD) as an agent against cholera via theoretical approaches. Computational analyses were conducted employing the B3LYP/6-311 + + 2d,2p level of theory, which provided substantial insights. Vibrational assignments via FT-IR spectroscopy confirmed the excellent agreement between the theoretical and reported experimental values, confirming the structural stability of the ligand. The electronic property analysis revealed slight variations in the electrophilicity index of the compound across solvents, with the highest (5.790 eV) in water and the lowest (5.753 eV) in the gas phase. Additionally, the high electronegativity values in all solvents, following the order of water (4.640 eV), DMSO (4.639 eV), ethanol (4.637 eV), and gas (4.584 eV), indicated ligand reactivity. Furthermore, molecular docking results indicated distinctive interactions between the ligand and the 1XTC and 6EHB cholera receptor proteins. A higher binding score was observed between the ligand and 1XTC, with a binding score of -7.6 kcal/mol, than between the ligand and 6EHB, with a binding score of -7.1 kcal/mol. Furthermore, the drug amoxicillin (AMOX) showed a comparable binding score of -7.8 kcal/mol for 1XTC and − 7.4 kcal/mol for 6EHB. The obtained results suggest the biological potential of TDZD as an anti-cholera agent and can be the foundation for further studies.