SYNTHESIS OF NOVEL IMIDAZOLE AND FUSED IMIDAZOLE DERIVATIVES AS CYTOTOXIC AND ANTIMICROBIAL AGENTS: MOLECULAR DOCKING AND BIOLOGICAL EVALUATION

  • Eatedal H Abd El-aal Zagazig University
  • Hanan A Abdel Fattah Zagazig University
  • Nermine A Osman Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
  • Israa A Seliem Zagazig University

Abstract

Objectives: The objective of this work is to synthesize novel imidazole and fused imidazole derivatives using 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) as key intermediate. The structure of the newly synthesized compounds was characterized using IR, 1HNMR, Mass spectroscopy, elemental analysis and some representative 13CNMR.

Methods: The target compounds were synthesized starting from 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) which prepared from the appropriate 5-arylidene-2-(methylthio)-3-phenyl imidazolin-4-ones (3a-c). Several synthetic pathways were be used for the preparation of the targets. Some of the newly synthesized compounds were evaluated for their cytotoxic activity against breast carcinoma and colon carcinoma cell lines. On the other hand, the antimicrobial activity evaluation of some newly prepared compounds was performed using cup plate diffusion method.

Results: Compound 5c was the most active one against breast carcinoma (IC50=3.3 ug/ml) and colon carcinoma cell lines (IC50=4.73 ug/ml) when compared with doxorubicin as standard. Molecular docking studies further supported the highest potency of 5c and further help understanding the various interactions between the ligand and enzyme active sites. On the other hand, the antimicrobial activity evaluation showed that most of the evaluated compounds exhibited broad spectrum activity.

Conclusion: The present work led to the development of promising antitumor compounds containing substituted imidazolidin-5-one or imidazotriazol-6-one skeletons. Compounds 5c showed the highest potency at low µg/ml level against breast MCF-7 and colon HCT116 cell lines. On the other hand, most of the newly synthesized compounds showed broad spectrum antimicrobial activity when cup plate diffusion method was performed.

 

Keywords: Imidazole, Fused imidazole derivatives, Cytotoxic, Antimicrobial activity

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El-aal, E. H. A., H. A. A. Fattah, N. A. Osman, and I. A. Seliem. “SYNTHESIS OF NOVEL IMIDAZOLE AND FUSED IMIDAZOLE DERIVATIVES AS CYTOTOXIC AND ANTIMICROBIAL AGENTS: MOLECULAR DOCKING AND BIOLOGICAL EVALUATION”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 11, Aug. 2015, pp. 36-45, https://innovareacademics.in/journals/index.php/ijpps/article/view/7381.
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