Hepatocellular carcinoma (HCC), one of the vascular solid tumors, accounts for 70%–85% of all malignant neoplasms of the liver burden worldwide. Although chemotherapy is the major treatment method for HCC patients, chemotherapeutic agents are known to have side effects or become ineffective through drug resistance mechanisms of tumor cells. Therefore, there is an urgent necessity to pay much attention to update and modify drug leads from the point of view of medicinal chemistry and drug design to fulfill more potent and effective therapies. By preliminary screening of indol-3-acrylamide type compounds synthesized by our group, 3-(1H-indol-3-yl)-N-(3,4,5-trimethoxyphenyl) acryl amide (SNB178) was identified as an inhibitor of cell proliferation
of different human cancer cell lines acting as an inhibitor of tubulin polymerization and an inducer of apoptosis. In this study, we designed and synthesized a novel series of (E)-indole-3-acrylamide derivatives with the prime aim of developing agents with potential anti-proliferative activity towards HCC cells. Cytotoxic activities of indole-3-acrylamide derivatives were analyzed by SRB assay and by real-time cell analyzer on HCC cell lines. Cell cycle analysis through flow cytometry and cell staining methods were used to determine the mechanism by which these derivatives were showing their anticancer effect. Among 48 tested derivatives, 3 of them were chosen to be further studied on each cell line. Flow cytometric analysis of cultured cells treated with these
molecules demonstrated that two of these compounds caused time dependent cell cycle arrest at the G2/M phase and also caused apoptotic cell death in Mahlavu and Snu-475 cell lines. Results were confirmed through western blot analysis where active molecules cause PARP cleavage in both cell lines indicating apoptosis and decrease in
Cdc2 (CDK1) and CyclinB1 levels addressing cell cycle arrest in G2/M phase

Conference Title

The XXIV EFMC International Symposium on Medicinal Chemistry

Conference Country

United Kingdom

Conference Date

Aug. 28, 2016 - Sept. 1, 2016

Conference Sponsor

EFMC

Additional Info

Conference Website