Design, synthesis and biological evaluation of some novel N′-(1,3-benzothiazol-2-yl)-arylamide derivatives as antibacterial agents

In the present work, we carried out hydroxybenzotriazole (HOBT) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl)-mediated synthesis of new N'-(1,3-benzothiazol-2-yl)-arylamides C1-18 in high yields under relatively milder reaction conditions using dimethyl formamide as solvent. Synthesized compounds were characterized by FTIR, H-1-NMR, C-13-NMR and HRMS spectral data. The MIC values of synthesized compounds C1-18 were determined by the broth microdilution method using Mueller Hinton medium. Tested compounds showed variable activity against the tested Gram-positive and Gram-negative bacterial strains. Compounds C-3, C-5, C-9, C13-15 and C-17 exhibited promising activity against Staphylococcus aureus NCIM 5021 with MIC values in the range of 19.7-24.2 mu M. Among all tested compounds, C-13 possessing thiophene ring attached to the benzothiazole moiety via amide linkage exhibited maximum activity against S. aureus NCIM 5022 with MIC of 13.0 mu M. Compound C-13 showed maximum activity against S. aureus ATCC 43300 with MIC of 15.0 mu M and exhibited bactericidal activity against this strain in minimum bactericidal concentration determination. This compound also eliminated S. aureus ATCC 43300 strain after 24-h exposure indicating its bactericidal activity. ADMET calculation showed favourable pharmacokinetic profile of synthesized compounds C1-18.