Synthesis, Structure‐Activity Relationship and Antimicrobial Evaluation of Methyl‐Substituted Tetrazoloquinoline‐Based Pyrazolinethioamides

A new series of pyrazolinethioamide and intermediate chalcone were synthesized from the tetrazoloqunoline molecule and the effect of these compounds on in‐vitro growth of microorganisms is studied. In‐vitro anti‐microbial activity was performed against S.aureus, S.epidermidis, P.mirabilis and E.coli. A number of analogues exhibited potent activity against all the bacterial strains. The SAR results indicate that the thioamide, methoxy group at C‐4 of phenyl ring and tetrazole unit play key roles for their bacterial inhibitory effect. This is further supported by the molecular modeling study of the crystal structure of PDB: 4Z7 M with compounds 5 b and 5 g. Compound 5 b showed potent antibacterial activity against S.aureus, S.epidermidis and moderate activity against E.coli with MIC values 6.25, 3.125, and 6.25 μg/mL, respectively. Compound 5 g showed potent antibacterial activity against S.epidermidis with MIC value 3.125 μg/mL but moderate activity against P.mirabilis and E. coli. Most promising compounds were tested for cytotoxic study by MTT assay on HepG2 cell line and the results showed that all the compounds offered remarkable >70 % viability up to the concentration of 100 μg/mL. tetrazoloquinolines based chalcones and their cyclized pyrazolinesthioamides analogues were synthesized and screened for their in‐vitro antibacterial activity. The 5‐(4‐methoxyphenyl)‐4,5‐dihydro‐3‐(7‐methyltetrazolo [1,5‐α] quinolin‐4‐yl) pyrazole‐1‐carbothioamide is the most potent bacterial inhibitor of the series with lowest cytotoxicity effect on HepG2 cell lines.