Synthesis, screening and docking analysis of novel benzimidazolium compounds as potent anti microbial agents targeting FtsZ protein

• Published in: Microbial pathogenesis 2018-11, Vol.124, p.258-265
• Main Authors: Sangeeta, G.P.V., Purna Nagasree, K., Risy Namratha, J., Krishna Kumar, Muthyala Murali
• Format: Article
• Language: English
• Subjects: Antimicrobial; Benzimidazolium; Molecular docking; Synthesis
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2018.08.046

The dominance of multi drug resistance in the clinically significant bacteria led to urgency in the development of new antibiotics with novel mechanism of action. Among the biochemical targets explored for selective toxicity, molecular mechanisms involving cell division remained focal point for novel antimicrobial drug discovery. For this purpose we have performed in-silico studies of FtsZ protein and obtained benzimidazolium compounds as potential hits. These molecules obtained in the dock results were synthesized via reacting benzimidazoles with appropriate benzyl halides. The structures of the synthesized compounds were confirmed by their 1H NMR, 13C NMR, IR and mass spectral data. These were evaluated for anti-microbial activity. Among the tested compounds B14, B15 and B20 have shown highest activity (MIC 5 μg/mL) against Staphylococcus aureus, Macrococcus caseolyticus, Escherichia coli and Pseudomonas aeruginosa. . Microscopic examination of drug-treated cultures of Staphylococcus aureus and Pseudomonas aeruginosa showed rod-shaped filamentous growth of the dividing cells, which is a characteristic feature of FtsZ inhibition. [Display omitted] •Novel FtsZ enzyme inhibitors with benzimidazole nucleus were designed and then docking analysis was carried out.•Hit molecules were synthesized and structures were confirmed by IR, NMR and Mass spectra.•They are evaluated for antimicrobial activity and anti fungal activity.•Cell divison inhibitory assay was performed as a proof of concept that it acts on FtsZ protein.