2. Academic Validation
  3. Synthesis, biological activities, and docking studies of d-pantolactone derivatives as novel FAS inhibitors

Synthesis, biological activities, and docking studies of d-pantolactone derivatives as novel FAS inhibitors

  • Bioorg Med Chem. 2019 Oct 15;27(20):115069. doi: 10.1016/j.bmc.2019.115069.
Hua Fang 1,  Jianlin He 2,  Tan Ran 2,  Hui Chen 3,  Wenhui Jin 3,  Bowen Tang 4,  Zhuan Hong 5,  Meijuan Fang 6
Affiliations

Affiliations

  • 1 Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; Xiamen Ocean Vocational College, Xiamen 361005, China; Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen 361005, China. Electronic address: hfang@tio.org.cn.
  • 2 Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen 361005, China.
  • 3 Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; Xiamen Ocean Vocational College, Xiamen 361005, China; Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen 361005, China.
  • 4 School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361005, China.
  • 5 Third Institute of Oceanography, Ministry of Natural Resources, Xiamen 361005, China; Xiamen Ocean Vocational College, Xiamen 361005, China; Fujian Collaborative Innovation Center for Exploitation and Utilization of Marine Biological Resources, Xiamen 361005, China. Electronic address: zhong@tio.org.cn.
  • 6 School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361005, China. Electronic address: fangmj@xmu.edu.cn.
PMID: 31492533 DOI: 10.1016/j.bmc.2019.115069
Abstract

A novel series of fatty acid synthase (FAS) inhibitors with D-(-)-pantolactone moiety and potential utility for the treatment of obesity were designed, synthesized and characterized, in which the structure of compound 3k was further confirmed by single X-ray diffraction. The mouse FAS inhibitory activity of synthesized compounds was evaluated. Major synthesized compounds (except 3g, 3i, 3k, 3l, and 3n) exhibited moderate FAS inhibitory properties with IC50 values in the range of 13.68 ± 1.52-33.19 ± 1.39 μM, reference inhibitor C75 has IC50 value of 13.86 ± 2.79 μM. Eight compounds (3c, 3d, 3e, 3f, 3j, 3m, 3q and 3r) also displayed inhibitory effect on lipid accumulation in human HepG2 cells. Additionally, the molecular docking study revealed that compound 3m having good inhibition activity against FAS and lipid accumulation also showed promising binding affinities with hFAS, while its binding model with hFAS (PDB ID: 4PIV) was different from that of reference compound C75.

Keywords

Fatty acid synthase (FAS); Lipid accumulation; Molecular docking; d-pantolactone derivatives.

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