Synthesis of Trifluoromethyl Benzimidazoles with Potential Anti-Microbial Activities

Abstract

A series of twenty-two new trifloromethyl benzimidazole derivatives were prepared based on azide and DCC coupling of 2-(2-(trifluoromethyl)-1H-benzoimidazol-1-yl) ethanoic acid derivatives with amino acids to give the amino acid esters; methyl 2-[(2-(2-(trifluoromethyl)-1H-benzimidazol-1-yl)acetamido] alkanoates. The amino acid esters reacted with hydrazine to produce the corresponding hydrazides that were finally condensed with p-fluorobenzaldehyde to obtain the hydrazones. The synthesized compounds were evaluated for their ability to bind to the crystal structure of E. coli (PDB = 1KZN) and the crystal structure of S. aureus (PDB = 1JIJ) bacteria, revealing good binding affinities. Notably, compounds 5e and 5k demonstrated primising interactive binding mode with the key amino acids like the co-crystallized ligands. As a result, they can be further tested as potent antimicrobial agents.