2. Academic Validation
  3. Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors

Synthesis and biological evaluation of quinoline analogues of flavones as potential anticancer agents and tubulin polymerization inhibitors

  • Eur J Med Chem. 2016 May 23:114:14-23. doi: 10.1016/j.ejmech.2016.02.069.
Nikta Shobeiri 1,  Maryam Rashedi 1,  Fatemeh Mosaffa 2,  Afshin Zarghi 3,  Morteza Ghandadi 2,  Ali Ghasemi 4,  Razieh Ghodsi 5
Affiliations

Affiliations

  • 1 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 2 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 4 Department of Pediatric Oncology-Hematology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 5 Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: ghodsir@mums.ac.ir.
PMID: 26974371 DOI: 10.1016/j.ejmech.2016.02.069
Abstract

A new series of 2-aryl-trimethoxyquinoline analogues was designed and synthesized as tubulin inhibitors using methoxylated Flavones as the lead compounds. The cytotoxic activity of the synthesized compounds was evaluated against four human Cancer cell lines including MCF-7, MCF-7/MX, A-2780, and A-2780/RCIS. All the alcoholic derivatives (6a-6e) showed significant cytotoxic activity with IC50 in the range of 7.98-60 μM. The flow cytometry analysis of the four human Cancer cell lines treated with 6e and 5b showed that 6e induced cell cycle arrest at G2/M phase and Apoptosis as well. The effect of quinolines on tubulin polymerization was also evaluated. Compound 6e that demonstrated the best antiproliferative activity in the series was identified as the most potent inhibitor of tubulin polymerization as well. Molecular docking studies of 6e into the colchicine-binding site of tubulin displayed possible mode of interaction between this compound and tubulin.

Keywords

Anticancer activity; Molecular docking; Quinolines; Resistant cancer cells; Tubulin polymerization.

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