Synthesis, Biological Evaluation and Molecular Docking Studies of Pyridine Incorporated Chalcone Derivatives as Anticancer Agents

Author(s): Sapavat Madhavi, Reddymasu Sreenivasulu, Md. Yousuf Ansari, Mohamed Jawed Ahsan, Rudraraju Ramesh Raju

Journal Name: Letters in Organic Chemistry

Volume 13 , Issue 9 , 2016

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Graphical Abstract:


Background: Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. If the spread is not controlled, it can result in death. Cancer is caused by inherited genetic mutations, hormones, and immune conditions. These factors may act together or in sequence to cause cancer. Ten or more years often pass between exposure to external factors and detectable cancer. Worldwide, one in seven deaths is due to cancer; cancer causes more deaths than AIDS, tuberculosis, and malaria combined. Chemotherapy was one of the important techniques for the treatment of cancer by using several chemotherapeutic agents. It involves the use of cytotoxic agents that destroy rapidly dividing cells. Despite of this progress, the discovery of most potent anti-cancer agents is a challenging issue in cancer chemotherapy without any side effects for the future generations.

Methods: The anticancer activity of the compounds was determined using MTT (3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) reduction assay. The molecular docking studies were performed using the Discovery Studio (DSv2.5) and GOLD installed in Window7. The X ray crystallographic structure of tubulin with colchicines as reference ligand (PDB: 1SA0) at resolution 3.58 Å with r value 0.233 (obs.) was downloaded from the protein data bank (PDB).

Results: Among the synthesized compounds, the compounds 10f, 10g, 10h, 10i and 10j showed more potent activity than control. The compound 10f, 10i and 10j showed comparatively higher anticancer activity than the standard (E7010) on all the three cell lines, while compound 10g and 10h showed higher activity than the standard (E7010) on ACHN and A549 cancer cell lines respectively. The order of anticancer activity of was found to be 10i > 10f > 10j > E7010. The current docking studies clearly presented the binding modes of the compounds in the active site of the colchicine binding site of the tubulin receptor.

Conclusion: The synthesis of novel pyridine based chalcones (10a-10j) was performed. All the compounds were completely characterized by spectroscopic data and elemental analysis. All these synthesized compounds were evaluated for anticancer potential against three human cancer cell lines (ACHN, MCF-7 and A-549). Among them compounds 10f, 10g, 10h, 10i and 10j were showed more potent activity than control drug.

Keywords: Chalcone, cytotoxicity, derricin, E7010, Lonchocarpin.

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Article Details

Year: 2016
Published on: 12 December, 2016
Page: [682 - 692]
Pages: 11
DOI: 10.2174/1570178613666161021105317
Price: $65

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