Hassan Mirzaei, Masoud Keighobadi, Saeed Emami,
Volume 26, Issue 146 (3-2017)
Abstract
Cancer is a complex and life-threatening disease involving uncontrollable cell proliferation, evading apoptosis, and metastasis. Despite recent developments in cancer chemotherapy, there are no effective broad spectrum anticancer agents that could selectively target cancer cells. Thus, designing and discovering new efficient and selective anticancer agents are urgent needs. It is important that new anticancer agents could act via apoptosis induction, since it has a critical role in control of cell proliferation. Chalcones are naturally occurring compounds possessing high degree of synthetic diversity for design of new leading bioactive compounds including anticancer agents. Chalcones are considered as promising anticancer agents against most human cancers with capability of inducing apoptosis in cancer cells. Furthermore, some clinically useful anticancer drugs show genotoxicity due to interaction with DNA, but chalcones with different mechanism may be devoid of this side effect. This review highlights the recently identified anticancer chalcones from naturally or synthetically origins that induce apoptosis in cancer cells. The diversity of scaffolds described in this review along with their structure-activity relationships could help medicinal chemists in development of new selective anticancer chalcones with improved potency.
Hassan Mirzaei, Mohammad Shokrzadeh, Saeed Emami,
Volume 27, Issue 154 (11-2017)
Abstract
Background and purpose: Chalcones are promising lead for anticancer drug design and discovery. Chalcones with different mechanisms including tubulin polymerization inhibition induce apoptosis in cancer cells. The aim of current work was synthesis of two indole-chalcone derivatives and investigation of their cytotoxic activity against cancer and normal cell lines, as well as molecular docking study with the proposed target tubulin.
Materials and methods: In this study, the indole-chalcone derivatives (3a and 3b) were prepared by the reaction of 4-methoxybenzaldehyde with 3-acetylindole or N-methyl-3-acetyl-indole in the presence of LiOH as catalyst. The pure compounds obtained were characterized by 1H NMR, IR, and Mass spectroscopy. The cytotoxic activity of synthesized compounds was tested using MTT assay toward four cancer cell lines (A549, MCF7, HepG2 and SKOV3) and a normal cell line (NIH3T3) in comparison with etoposide. Molecular docking was performed by using AutoDock 4.2 software to evaluate potential mechanism and interactions of chalcone compounds with the tubulin (1SA0) binding site.
Results: The 1H NMR spectra of compounds showed two doublets related to the vinylic protons with coupling constant value of 15.6 Hz, demonstrating trans configuration of the compounds. Cytotoxicity assay showed that these compounds had a significant effect against viability of cancer cells. The compound 3b with IC50 value of 8.1 μg/ml against HepG2 had the most potent cytotoxic effect. Furthermore, this compound had no significant cytotoxic effect against normal cell line. Docking analysis showed that compound 3b is bound to the colchicine binding site of tubulin via hydrogen and hydrophobic interactions.
Conclusion: The indole-derived chalcones had a significant selective cytotoxic effect against cancer cells. The N-methyl-indole analog 3b showed better profile of activity against tested cell lines. This analog can be considered as a lead compound for further optimization and development of potent anticancer agents.
