Design, synthesis, DNA, and BSA-binding of 5-mercapto-1,3,4-thiadiazol and 5-methylisoxazol derivatives: DFT, Molecular dockings, ADMET, and drug-likeness profiles

A new series of 5-mercapto-1,3,4-thiadiazol (SH-2NBA, SH-3NBA, and SH-4NBA), and 5-methylisoxazol (OX-2NBA, OX-3NBA, and OX-4NBA) bearing mercapto or methyl moieties were synthesized by the reaction of 2,3,4-nitrobenzoyl chloride with 5-amino-1,3,4-thiadiazole-2-thiol and 3-amino-5-methylisoxazole in the presence of toluene-TEA. Their structures were characterized with H-1 NMR, C-13 NMR, UV, and FT-IR. These compounds possess a broad variety of functional activities and have become the subject of considerable growing interest for designing synthesis. The quantum mechanical computations were performed at B3LYP/6-311G** level in both the gas and DMSO simulation environments, for structural and spectroscopic confirmation, then evaluation of the chemical reactivity behavior of the thiadiazol and oxazol isomers. The solubility in octanol and water, ADMET, and drug-likeness properties were elucidated to predict the possible pharmacokinetic profiles, drug-likeness properties, and bioavailability indexes, which would provide a deep insight into early-stage drug-design works. Additionally, BSA binding and DNA binding properties of the molecules were evaluated using spectrophotometric methods. BSA binding properties were analyzed by the Stern-Volmer method, while DNA binding analyses were performed by the Benesi-Hildebrand method. Additionally, the details of both BSA and DNA binding properties were evaluated using molecular docking methods.