Design, synthesis, characterization and computational docking studies of novel sulfonamide derivatives

Abstract

This study reports three novel sulfonamide derivatives 4-Chloro-N-[(4-methylphenyl) sulphonyl]-N-propyl ben- zamide (1A), N-(2-hydroxyphenyl)-4-methyl benzene sulfonamide (1B) and 4-methyl-N-(2-nitrophenyl) ben- zene sulfonamide (1C). The compounds were synthesised from starting material 4-methylbenzenesulfonyl chlo- ride and their structure was studied through 1H-NMR and 13C-NMR spectra. Computational docking was per- formed to estimate their binding energy against bacterial p-amino benzoic acid (PABA) receptor, the dihydrop- teroate synthase (DHPS). The derivatives were tested in vitro for their antimicrobial activity against Gram+ and Gram- bacteria including E. coli, B. subtilis, B. licheniformis and B. linen. 1A was found active only against B. linen; 1B was effective against E. coli, B. subtilis and B. linen whereas 1C showed activity against E. coli, B. li- cheniformis and B. linen. 1C showed maximum activity with minimum inhibitory concentration (MIC) of 50, 100 and 150 µg/mL against E. coli, B. licheniformis and B. linen respectively. 1C exhibited maximum affinity to DHPS with binding free energy of -8.1 kcal/mol. It enriched in the top 0.5 % of a library of 7663 compounds, ranked in order of their binding affinity against DHPS. 1C was followed by 1B which showed a moderate to low level MIC of 100, 250 and 150 µg/mL against E. coli, B. subtilis and B. linen respectively, whereas 1A showed a moderate level MIC of 100 µg/mL but only agai st B. linen. These derivatives may thus serve as potential anti-bacterial alternatives against resistant pathogens.