Synthesis,Characterization,Molecular Docking Studies and Biological Evaluation of Some Conjugated Quinazoline-Sulfonamide Scaffold

摘要

A series of sulfonamides containing 4-aminoquinazoline scaffolds 7a-7 l was synthesized,characterized and evaluated for their in vitro antitubercular,antimicrobial and anticancer activity.The compounds with 4-nitrophenyl (7c),3-trifluoromethylphenyl (7f) and 5-chloro-pyridin-2-yl (7h) derivatives have shown potent antitubercular activity against Mycobacterium tuberculosis H37Rv strain and the activity was two-fold higher than the standard drug Ciprofloxacin.The compounds with 4-chlorophenyl (7a),pyridin-2-yl (7g),5-chloro-pyridin-2-yl (7h) and pyrimidin-2-yl (7i,7j and 7k) derivatives were observed as excellent antimicrobial agents.The preliminary toxicity of selected potent compounds was also tested on Red Blood Cells by hemolytic assay and found to be non-toxic even at higher concentrations.Compounds with 4-nitrophenyl (7c) and 4-fluorophenyl (7e) substitutions emerged as potent molecules against MDA-MB-231 cell line.ADME (Absorption,Distribution,Metabolism and Excretion) screening study revealed that the compounds are strong candidates for antitubercular activity with good ADME parameters.In addition,the structure and antitubercular activity relationship were further supported by molecular docking studies of the active compounds against the DNA topoisomerase II (5BTC) enzyme of M.tuberculosis.