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...

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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

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spelling	doaj-80fe24d922bf402fb352b6d091e38b552020-11-25T01:54:25ZengMDPI AGMolecules1420-30492019-09-012417318010.3390/molecules24173180molecules24173180Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase InhibitorsZhan-Fang Fan0Sai-Tim Ho1Rui Wen2Ya Fu3Lei Zhang4Jian Wang5Chun Hu6Pang-Chui Shaw7Yang Liu8Mao-Sheng Cheng9Key Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaSchool of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Structure-Based Drugs Design and Discovery (Ministry of Education), School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, ChinaBased 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 μM. 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.https://www.mdpi.com/1420-3049/24/17/3180human telomerase holoenzymeflavonoidantiproliferative activitymolecular modeling
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Zhan-Fang Fan Sai-Tim Ho Rui Wen Ya Fu Lei Zhang Jian Wang Chun Hu Pang-Chui Shaw Yang Liu Mao-Sheng Cheng
spellingShingle	Zhan-Fang Fan Sai-Tim Ho Rui Wen Ya Fu Lei Zhang Jian Wang Chun Hu Pang-Chui Shaw Yang Liu Mao-Sheng Cheng Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors Molecules human telomerase holoenzyme flavonoid antiproliferative activity molecular modeling
author_facet	Zhan-Fang Fan Sai-Tim Ho Rui Wen Ya Fu Lei Zhang Jian Wang Chun Hu Pang-Chui Shaw Yang Liu Mao-Sheng Cheng
author_sort	Zhan-Fang Fan
title	Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors
title_short	Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors
title_full	Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors
title_fullStr	Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors
title_full_unstemmed	Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors
title_sort	design, synthesis and molecular docking analysis of flavonoid derivatives as potential telomerase inhibitors
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2019-09-01
description	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 μM. 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.
topic	human telomerase holoenzyme flavonoid antiproliferative activity molecular modeling
url	https://www.mdpi.com/1420-3049/24/17/3180
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Design, Synthesis and Molecular Docking Analysis of Flavonoid Derivatives as Potential Telomerase Inhibitors

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