Design, synthesis, and biological activity evaluation of new tankyrase-2 directed inhibitors

  • Chem Biol Drug Des. 2023 Oct 10. doi: 10.1111/cbdd.14360.
Xiaoli Zhang  1 ,  Wan Pang  1 ,  Tang Li  1 ,  Taofeng Lin  1 ,  Juanchan Yuan  1 ,  Songhui Xu  2
Affiliations
  • 1. College of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China.
  • 2. Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
PMID: 37814809 DOI: 10.1111/cbdd.14360
Abstract

A new series of Flavonoids and Quinolone derivatives were designed, synthesized and, evaluated for their biological activity. Among them, compound 14e showed better inhibition potency against TNKS2 in comparison with G007-LK, one of the most potent preclinical stage TNKS inhibitor. Molecular docking results showed that 14e occupied both the adenosine and nicotinamide pockets and formed a hydrogen bond with Met1054 of TNKS2. This study provides a lead for the design and discovery of potent and selective TNKS2 inhibitors.

Keywords
flavonoids and quinolone derivatives; molecular docking; molecular dynamics, TNKS2 inhibitors.
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