New Insights Towards 1,4-Benzodiazepines from Curcumin. Design, Synthesis and Antimicrobial Activities

Abstract

Background: Curcumin is a safe, versatile natural product with unlimited number of biological activities and a precursor for various heterocyclic compounds.

Objective: The present study was aimed to the development of a curcumin based antimicrobial reagent with high potency against gram-positive and gram-negative bacteria.

Methods: Herein we report a simple and convenient one step method for synthesizing a series of 1,4-benzodiazepines via condensation cyclization reaction between curcumin and various 1,2- phenylenediamine in refluxed ethanol.

Results: A series of new 1,4-benzodiazepins were synthesized and their structures were supported by FT-IR, 1H NMR, 13C NMR, and mass spectral analysis. Synthesized 1,4-benzodiazepins were evaluated for their in vitro antimicrobial activity against gram positive (S. aureus and S. epidermidis) and gram negative (E. coli and P. aeruginosa) bacteria. They exhibited low to high potency against the tested organisms. In particular, dichlorinated 1,4-benzodiazepine 9 exhibited a remarkable potency against the gram-positive bacteria S. aureus (MIC: 3.125 μg mL-1, MBC: 12 μg mL-1). It showed a higher potency than most of the tested reference drugs. Compound 9 showed the medium activity against E. coli. Genotoxic study revealed that, benzodiazepines 9 attacked the DNA of E. coli strains and damaged it. The potency of compound 9, could be attributed to the multiple chlorine atoms present on the aromatic ring.

Conclusion: Some of the synthesized curcumin based benzodiazepines showed excellent potency against gram positive bacteria. These benzodiazepines could be a great candidate as a future antimicrobial agent.

Keywords: Disc diffusion; antimicrobial; biological activities; curcumin; diazepine; genotoxicity.