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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/17/3180 |
| _version_ | 1819117929436807168 |
|---|---|
| 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 |
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T05:40:47Z |
| format | Article |
| id | doaj.art-80fe24d922bf402fb352b6d091e38b55 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T05:40:47Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-80fe24d922bf402fb352b6d091e38b552022-12-21T18:37:11ZengMDPI 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 |
| 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 |
| title | 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_short | 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 |
| topic | human telomerase holoenzyme flavonoid antiproliferative activity molecular modeling |
| url | https://www.mdpi.com/1420-3049/24/17/3180 |
| work_keys_str_mv | AT zhanfangfan designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT saitimho designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT ruiwen designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT yafu designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT leizhang designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT jianwang designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT chunhu designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT pangchuishaw designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT yangliu designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors AT maoshengcheng designsynthesisandmoleculardockinganalysisofflavonoidderivativesaspotentialtelomeraseinhibitors |