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

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...

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Bibliographic Details
Published in:Chemical biology & drug design 2024-01, Vol.103 (1), p.e14360-n/a
Main Authors: Zhang, Xiaoli, Pang, Wan, Li, Tang, Lin, Taofeng, Yuan, Juanchan, Xu, Songhui
Format: Article
Language:English
Subjects:
flavonoids and quinolone derivatives
molecular docking
Molecular Docking Simulation
molecular dynamics, TNKS2 inhibitors
Tankyrases - chemistry
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Summary: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. Compared with flavonoids, quinolones, and G007‐LK, compound 14e showed the best inhibition potency against TNKS2, as it simultaneously occupied both the adenosine and nicotinamide pockets and formed a hydrogen bond with the amino group of Met1054.
ISSN:1747-0277
1747-0285
DOI:10.1111/cbdd.14360