Title:New Insights Towards 1,4-Benzodiazepines from Curcumin. Design, Synthesis and Antimicrobial Activities
VOLUME: 16 ISSUE: 8
Author(s):Othman Hamed*, Oswa Fares, Shaima Taleeb, Ghaleb Adwan, Haythem Saadeh, Shehdeh Jodeh and Manuel Algarra
Affiliation:Department of Chemistry, College of Science, An-Najah National University, Nablus, Department of Chemistry, College of Science, An-Najah National University, Nablus, Department of Chemistry, College of Science, An-Najah National University, Nablus, Department of Biology, College of Science, An-Najah National University, Nablus, Department of Chemistry, College of Science, United Arab Emirate University, P.O. Box 15551, Al Ain, Department of Chemistry, College of Science, An-Najah National University, Nablus, CQM-Centro de Quimica da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal
Keywords:Disc diffusion, diazepine, curcumin, genotoxicity, antimicrobial, biological 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.
