الفهرس 
Title : Synthesis, docking simulation, and biological activity studies of some unsaturated carbonyl derivatives
AbstractOnly 14 pages are availabe for public view
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Abstract
A new series of cyanoacrylamide was synthesized and characterized by
different physicochemical and multispectral investigations. The cytotoxic
potential of these compounds was assessed against different human cancer
cell lines (HCT116, MCF-7, and Hep2). 4-(piperidin-1-yl)phenyl
derivative 5g was selected as it showed the most promising cytotoxic activity
against the HCT116 and MCF7 cell lines with IC50 values ranging from 32 to
50 µM. . Moreover, compound 5g cytotoxicity against normal human cells
(WI-38) was evaluated, and the results revealed that this compound has low
toxicity. Investigation of the apoptotic activity of the most active compound
revealed that compound 5g could induce both the early and the late apoptosis
of HCT116. Further mechanistic study of the HCT116 cell cycle confirmed
the spectacular cytotoxic and apoptotic effects of compound 5g.
Compound 5g showed a pronounced increase in cells in the G2/M and S
phases with a concomitant reduction of cells in the G0-G1 phase. This
compound also induced a significant increase in the caspase-3 activities,
remarkable downregulation of the Bcl-2 (at mRNA and protein level), CDK1
and CDK2 (at mRNA level), and significant upregulation of the Bax at
mRNA and protein level using qRT-PCR and ELISA. Furthermore, 5g also
proved to have a good DNA binding affinity using UV-Vis measurements.
Prediction of ADMET properties and oral toxicity of the drug-likeness
features of compound 5g were carried out using online software. Moreover, a
molecular docking study for compound 5g was performed to predict their
binding affinities toward DNA and the active site of different protein sets
(Bcl2, Bcl-xl, Mcl-1, XIAP, survivin, CDK1, and CDK2). Results of
molecular docking were strongly correlated with that of the cytotoxicity
study.