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

Abstract

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 mg/mL, respectively. Compound 5 g showed potent antibacterial activity against S.epidermidis with MIC value 3.125 mg/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 mg/mL.

Synthesis of 4-(Phenylchalcogenyl)tetrazolo[1,5-a]quinolines by Bicyclization of 2-Azidobenzaldehydes with Phenylchalcogenylacetonitrile

“…Tetrazoloquinolines are molecular hybrids that contain both quinoline and tetrazole systems in the same molecule, and they have received much attention due to their biological activities and synthetic usefulness [ 8 , 9 , 10 , 11 ]. Despite the significant advances toward the synthesis of new azaheterocycles, the need for a new study on the combinations of substrates for the synthesis of new tetrazoloquinolines and more complex structures is still an open issue.…”

“…In this context, chalcogen–tetrazolo[1,5- a ]quinolines constitute an interesting class of molecules, which combine the importance of a tetrazoloquinoline nucleus [ 8 , 9 , 10 , 11 ] with an organochalcogen moiety [ 12 , 13 , 14 ]. Selenium and sulfur are important essential elements, playing important roles in metabolic pathways [ 15 , 16 , 17 , 18 , 19 , 20 ], and the interest in chalcogen chemistry [ 21 , 22 , 23 ] and pharmacology [ 24 , 25 , 26 , 27 ] has increased in this century.…”