New triazole based oxadiazolo/thiadiazolo–phthalazines as potent antimycobacterial agents: Design, synthesis, molecular modelling and in silico ADMET profiles

Abstract The study of the chemical and biological properties of molecules simultaneously comprising various heterocycles, such as fused 1,3,4–oxadiazolyl–1,2,3–triazoles and 1,2,4–triazolyl–1,3,4–thiadiazole have been conducted as part of our ongoing research in the field of medicinal and organic chemistry. In this study, we performed ligand–based pharmacophore modelling as a promising design strategy of substituted phthalazinone derivatives ( 5 and 7 ). These were synthesized from key intermediate mercapto‐containing oxadiazo‐phthalazinone derivative 2 . The synthesized compounds were characterized by IR, 1 H and 13 C NMR, elemental analysis and mass spectrometric techniques. In preliminary antibacterial studies, analogues 5 d , 5 f , 7 a and 7 d were found to be most effective against S. epidermidis , whereas 5 d displayed excellent activity against P. aeruginosa microorganism. Later, explored the probable key active site and inhibitors of Cytochrome P450 CYP121A1 interactions from M. tuberculosis H 37 Rv based antitubercular drug candidate with 5O4K protein and ligand 7 b possesses highest hydrophobic amino acid residues. The physicochemical and medicinal properties were also evaluated using SwissADME and ADMETlab2.0 web to function as effective oral bioavailability medications.