2. Academic Validation
  3. Design, synthesis and biological evaluation of novel chroman derivatives as non-selective acetyl-CoA carboxylase inhibitors

Design, synthesis and biological evaluation of novel chroman derivatives as non-selective acetyl-CoA carboxylase inhibitors

  • Bioorg Chem. 2020 Aug;101:103943. doi: 10.1016/j.bioorg.2020.103943.
Qiangqiang Wei 1,  Liankuo Mei 2,  Pan Chen 1,  Xinrui Yuan 2,  Huibin Zhang 3,  Jinpei Zhou 4
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 2 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
  • 3 Center of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: zhanghb80@163.com.
  • 4 Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: jpzhou668@163.com.
PMID: 32554277 DOI: 10.1016/j.bioorg.2020.103943
Abstract

Acetyl-CoA carboxylases (ACCs) are the rate-limiting Enzymes in the de no lipogenesis, which play an important role in the synthesis and oxidation of fatty acid. Recent research reveals that ACCs are tightly relevant to many kinds of metabolic diseases and cancers. In this study, we synthesized a series of chroman derivatives and evaluated their ACCs inhibitory activities, obtaining compound 4s with IC50 value of 98.06 nM and 29.43 nM of binding activities in ACC1 and ACC2, respectively. Compound 4s exhibited the most potent anti-proliferation activity against A549, H1975, HCT116 and H7901 cell lines (values of IC50: 0.578 μΜ, 1.005 μΜ, 0.680 μΜ and 1.406 μΜ, respectively). Docking studies were performed to explain the structure-activity relationships. These results indicate that compound 4s is a promising ACC1/2 inhibitor for the potent treatment of Cancer.

Keywords

Acetyl-CoA inhibitors; Anticancer; Molecular docking.

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