Synthesis of Novel Antimicrobial Indazole-Linked 1,2,4-Triazolylthiadiazole and 4-Thiazolidinone Derivatives and Study of Their Molecular Modelling

Indazole-based synthetic and natural products with inherent antimicrobial activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of 1,2,4-triazolyl-1,3,4-thiadiazoles, 4-thiazolidinones and screened for their in vitro antibacterial effect against different microorganisms, and antitubercular activity against M. tuberculosis H 37 RV. The biological studies revealed that such indazole analogues as 4-methoxyphenyl-4-thiazolidinone, 4-hydroxyphenyl-1,2,4-triazolyl-1,3,4-thiadiazole, 3-nitrophenyl-1,2,4-triazolyl-1,3,4-thiadiazole are active against S. epidermidis , and 3-nitrophenyl-1,2,4-triazolyl-1,3,4-thiadiazole, 2-chlorophenyl-1,2,4-triazolyl-1,3,4-thiadiazole exhibited excellent antitubercular activity against M. tuberculosis H 37 RV. In addition, the docking studies revealed the potential ligand 4-hydroxyphenyl-1,2,4-triazolyl-1,3,4-thiadiazole shows a highest amino acid interactions Arg43(A), Asp42(A), Phe41(A), Val65(A), Ile122(A), Ile16(A), Leu63(A), Gly14(A), Ile95(A), Thr39(A), Ser13(A) against M. tuberculosis enoyl reductase InhA of GSK625 (5JFO) and binding energy –8.48 kcal/mol. All the prepared compounds possess highest drug likeness properties and considering their bioactivity potentials, perhaps highly substitute indazole functionalized compounds could be the future antibiotics.