Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors

Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors

Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound <b>5c</b> exhibited the most potent inhibitory ac...

Full description

Bibliographic Details
Main Authors: Zhan-Fang Fan, Sai-Tim Ho, Rui Wen, Ya Fu, Lei Zhang, Jian Wang, Chun Hu, Pang-Chui Shaw, Yang Liu, Mao-Sheng Cheng
Format: Article
Language:English
Published: MDPI AG 2019-09-01
Series:Molecules
Subjects:
human telomerase holoenzyme
flavonoid
antiproliferative activity
molecular modeling
Online Access:https://www.mdpi.com/1420-3049/24/17/3180
Description
Summary:Based on the structural scaffolds of natural products, two series of flavonoid derivatives, for a total of twelve compounds, were designed and synthesized as potential human telomerase inhibitors. Using a modified TRAP-PCR assay, compound <b>5c</b> exhibited the most potent inhibitory activity against human telomerase with an IC<sub>50</sub> value of less than 50 &#956;M. In vitro, the results demonstrated that compound <b>5c</b> had potent anticancer activity against five classes of tumor cell lines. The molecular docking and molecular dynamics analyses binding to the human telomerase holoenzyme were performed to elucidate the binding mode of active compound <b>5c</b>. This finding helps the rational design of more potent telomerase inhibitors based on the structural scaffolds of natural products.
ISSN:1420-3049

Similar Items