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Molecular Studies on Novel Antitumor Bis 1,4-Dihydropyridine Derivatives Against Lung Carcinoma and Their Limited Side Effects On Normal Melanocytes.
Anti-cancer Agents in Medicinal Chemistry 2018 October 19
Novel 1,4-dihydropyridine derivatives were synthesized and their structures were confirmed by different spectral tools. The newly synthesized compounds were screened on two different tumor cell lines (A549 and MCF7). In an attempt to know the mechanism of action of the synthesized compounds as cytotoxic agents, we studied their effect on lung carcinoma cell line (A549) for its better cytotoxicity. The molecular data showed that all compounds caused cell cycle arrest at G1 phase and this confirmed theoretically by molecular docking studies on CDK2 and slightly increased the percentage of early apoptosis with no detectable DNA ladder characteristic of apoptotic cell death. The four compounds induced the up-regulation of Bax gene and the down-regulation of P53and Bcl2 genes. The activity of caspase 3 was slightly higher than control for compounds7 and 10 and slightly lower than control for compounds 8 and 9. We also studied the effect of compound 8 on the normal cell line (HFB4) after its treatment with genotoxic factor (H2O2) and we noticed that compound 8 decreased the percentage of apoptosis that was induced by H2O2. The new compounds have limited side effects on normal cells and could be used as complementary drugs to reduce the harmful effects of other chemotherapeutic agents.
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