TY - JOUR
T1 - New insights towards 1,4-benzodiazepines from curcumin. Design, synthesis and antimicrobial activities
AU - Hamed, Othman
AU - Fares, Oswa
AU - Taleeb, Shaima
AU - Adwan, Ghaleb
AU - Saadeh, Haythem
AU - Jodeh, Shehdeh
AU - Algarra, Manuel
N1 - Funding Information:
A new series of benzodiazepines were synthesized with a quantitative yield using a simple procedure. The benzodiazepines were synthesized from reacting curcumin or tetra-hydrocurcuminoid ith w ariouvs ,2-d1amiino compounds. The structures of the synthesized benzodiazepines were evaluated by various spectroscopic ecthniques. hTe ntaibac-terial activities of the newly prepared benzodiazepines were evaluated against two gram-positive and two gram-negative bacteria. The curcumin benzodiazepines showed moderate to good activity against most tested bacteria. Among the tested compounds diazepinse 3 and 4ndadichlorinated benzodiazepine 9 howsed he tighest pencoy agatinst the gram-positive bacteria S. aureus. The tetrahydrocurcuminoid ebn-zodiazepines showed low to good activity against tested bac- Deanship of Scientific Research, An-Najah National University, Nablus, Palestine. Grant number project No. ANNU-1718-Sc023.
Funding Information:
The authors would like to acknowledge the Deanship of Scientific Research at An-Najah National University for funding and support of this work through the project No. ANNU-1718-Sc023.
Publisher Copyright:
© 2020 Bentham Science Publishers.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Antimicrobial
KW - Biological activities
KW - Curcumin
KW - Diazepine
KW - Disc diffusion
KW - Genotoxicity
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U2 - 10.2174/1573406415666190826160251
DO - 10.2174/1573406415666190826160251
M3 - Article
C2 - 31448712
AN - SCOPUS:85095413681
SN - 1573-4064
VL - 16
SP - 1112
EP - 1123
JO - Medicinal Chemistry
JF - Medicinal Chemistry
IS - 8
ER -