2. Academic Validation
  3. Design, synthesis and biological evaluation of 7-(aryl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline derivatives as potential Hsp90 inhibitors and anticancer agents

Design, synthesis and biological evaluation of 7-(aryl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline derivatives as potential Hsp90 inhibitors and anticancer agents

  • Bioorg Med Chem. 2017 Feb 1;25(3):1294-1302. doi: 10.1016/j.bmc.2016.12.050.
Sina Omid Malayeri 1,  Khalil Abnous 2,  Atefeh Arab 3,  Maryam Akaberi 4,  Soghra Mehri 2,  Afshin Zarghi 5,  Razieh Ghodsi 6
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 Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3 Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 4 Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 5 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 6 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: 28073608 DOI: 10.1016/j.bmc.2016.12.050
Abstract

A new series of quinoline analogues was designed and synthesized as HSP90 inhibitors. The cytotoxic activity of the synthesized compounds was evaluated against three human Cancer cell lines including MCF-7 (human breast Cancer cells), DU145 (human prostate Cancer cell lines), and A549 (adenocarcinomic human alveolar basal epithelial cells). Some of our compounds (13a-13f) showed significant cytotoxic activity on MCF-7 cells. The most potent anti-proliferative compounds were also tested against Her2, a client protein of HSP90. Compound 13d that demonstrated the highest antiproliferative activity in the series, was found the most potent one for both Her2 protein degradation and HSP70 protein induction as well. Molecular modeling studies displayed possible mode of interaction between this compound and N-terminal ATP-binding site of HSP90.

Keywords

Anti-cancer activity; Heat Shock Protein 90; Her2; Hsp90 inhibitor; Molecular docking; Quinolines.

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