Synthesis, Chemotherapeutic Screening and Docking Studies of NSAID Inserted Peptide‐Triazole Hybrid Molecules

Abstract

A series of peptide based new tryptophan-1,2,3-triazole-naproxen derivatives were explored as prospective antibacterial / cytotoxic agents. These derivatives were prepared via a multi-step method involving CuAAC as a key step and characterized by spectral data. The synthesized derivatives were evaluated for their antimicrobial activities against one Gram-positive (S. aureus) and three Gram-negative (E. coli, K. pneumoniae and P. vulgaris) bacteria using an agar-well diffusion protocol where amoxycillin was used as a reference compound. Most of these compounds showed antibacterial activities when tested at 0.4 mg / 50 μl concentration. Compound 9 e i. e. N-(1-amino-1-oxo-3-phenylpropan-2-yl)-3-(1-((1-(2-((2-chlorophenyl)amino)-2-oxoethyl)-1H-1,2,3-triazol-4-yl)methyl)-1H-indol-3-yl)-2-(2-(6-methoxynaphthalen-2-yl)propanamido)propanamide exhibited good activities against all the strains. The potential DNA gyrase inhibitory activity of this compound was investigated by molecular docking studies carried out using Autodock Vina software. Compound 9 e showed an impressive ΔGbind of −10.0 kcal/mol. The cytotoxicity of the obtained compounds was also assessed against A549 cancer cell line (human lung carcinoma) by an MTT assay. Several of these compounds showed promising activity while 9 e showed lowest IC50 value. A brief SAR for both antibacterial / cytotoxic activities of compounds tested is presented. Overall, compound 9 e has emerged as an initial hit molecule for further study.