Synthesis, Anticancer Activity and Molecular Modeling Studies of Novel Chalcone Derivatives Containing Indole and Naphthalene Moieties as Tubulin Polymerization Inhibitors

摘要

Eighteen novel chalcone derivatives containing indole and naphthalene moieties (2–19) were synthesized and characterized by sup1/supH-NMR, sup13/supC-NMR and high resolution (HR)-MS spectra. All compounds were evaluated for their in vitro cytotoxic potential against human hepatocellular carcinoma (HepG2), human colon carcinoma (HCT116) and human breast adenocarcinoma (MCF-7) cell lines. Among them, compound 2, 3, 4 and 7 showed potent activities against tested cancer cell lines. More significantly, compound 7 exhibited the most potent cytotoxic activity against HepG2, HCT116 and MCF-7 with ICsub50/sub values of 0.65, 1.13 and 0.82?μM, respectively. Furthermore, flow cytometry analysis indicated that compound 7 arrested cancer cells in G2/M phase. The compound 7 also displayed significant inhibition of tubulin polymerization (ICsub50/sub?=?3.9?μM). Finally, molecular docking studies were performed to explore the possible interactions between compound 7 and tubulin binding pockets.