Four-Component Synthesis of 1,2-Dihydropyridine Derivatives and their Evaluation as Anticancer Agents

Title:Four-Component Synthesis of 1,2-Dihydropyridine Derivatives and their Evaluation as Anticancer Agents

Volume: 8 Issue: 3

Author(s): Mohamed A. O. Abdel-Fattah, Mahmoud A. M. El-Naggar, Rasha M. H. Rashied, Bernard D. Gary, Gary A. Piazza and Ashraf H. Abadi

Affiliation:

Keywords: Multicomponent reactions, 1, 2-dihydropyridine, cancer, malononitrile, dihydropyridine, cyanoacetate, acetophenone, isosteric, oxopyridines, antimicrobials

Abstract: Two series of compounds with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3-carbonitriles and their isosteric imino derivatives were synthesized through a one pot reaction of acetophenone, aldehyde and ammonium acetate with ethyl cyanoacetate or malononitrile, respectively. The synthesized compounds were evaluated for tumor cell growth inhibitory using the human HT-29 colon and MDA-MB-231 breast tumor cell lines. Compound 4-(2- Ethoxyphenyl)-2-imino-6-(4-fluorophenyl)-1,2-dihydropyridine-3 carbonitrile (6) showed IC50 value of 0.70 μM versus HT-29. Meanwhile, compound 4-(2-Hydroxyphenyl)-2-imino-6-(4-fluorophenyl)-1,2-dihydropyridine-3-carbonitrile (4) showed IC50 value of 4.6 μM versus MDA-MB-231. Docking compound 10 to possible molecular targets, survivin and PIM1 kinase showed appreciable interactions with both, which suggest possible targets for the antitumor activity of this novel class of anticancer compounds.

Cite this article as:

A. O. Abdel-Fattah Mohamed, A. M. El-Naggar Mahmoud, M. H. Rashied Rasha, D. Gary Bernard, A. Piazza Gary and H. Abadi Ashraf, Four-Component Synthesis of 1,2-Dihydropyridine Derivatives and their Evaluation as Anticancer Agents, Medicinal Chemistry 2012; 8 (3) . https://dx.doi.org/10.2174/1573406411208030392