Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents
Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed 5j a higher binding affinity for tubulin.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Future medicinal chemistry - 11(2019), 23 vom: 31. Dez., Seite 3015-3027 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lu, Yapeng [VerfasserIn] |
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| Links: |
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| Themen: |
2,4,5-trideoxyhexopyranosides |
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| Anmerkungen: |
Date Completed 15.07.2020 Date Revised 15.07.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2018-0593 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM302725865 |
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| 100 | 1 | |a Lu, Yapeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Divergent de novo synthesis of 2,4,5-trideoxyhexopyranosides derivatives of podophyllotoxin as anticancer agents |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 15.07.2020 | ||
| 500 | |a Date Revised 15.07.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Identification of new anticancer glycosidic derivatives of podophyllotoxin. Methods: 14 podophyllotoxin D- and L-monosaccharides have been synthesized in three steps employing de novo glycosylation strategy, and their abilities to inhibit the growth of HeLa, HepG2, MCF-7, A549 and MDA-MB-231 cancer cells were investigated by MTT assay. Molecular docking study of compound 5j with tubulin was performed. Immunofluorescence was applied for detecting the inhibitory effect of 5j on tubulin polymerization. Results & conclusion: Most of synthesized compounds showed strong cytotoxicity activity against five cancer cell lines. Compound 5j possessed the highest cytotoxicity with the IC50 values from 41.6 to 95.2 nM, and could concentration-dependently inhibit polymerization of the microtubule cytoskeleton of MCF-7 cells. Molecular docking disclosed that sugar moiety-dedicated hydrogen bond endowed 5j a higher binding affinity for tubulin | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a 2,4,5-trideoxyhexopyranosides | |
| 650 | 4 | |a anticancer agents | |
| 650 | 4 | |a de novo synthesis | |
| 650 | 4 | |a podophyllotoxin | |
| 650 | 4 | |a tubulin | |
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| 700 | 1 | |a Wang, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xinyang |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Haoliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yu |e verfasserin |4 aut | |
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