Bioinspired computational design of lankacidin derivatives for improvement in antitumor activity
Background: The 17-membered polyketide, lankacidin C, exhibits considerable antitumor activity as a microtubule stabilizer by binding to the paclitaxel binding site. Method: Esterification of the C-7/C-13 hydroxyl in lankacidin C was performed with acetyl, cinnamoyl and hydrocinnamoyl groups and their antitumor activity was assessed to improve the cytotoxicity of lankacidins through bioinspired computational design. Results: Compared with the cytotoxicity of parent lankacidin C against the HeLa cell line, 13-O-cinnamoyl-lankacidin C demonstrated sevenfold higher cytotoxicity. Furthermore, 7,13-di-O-cinnamoyl-lankacidin C exhibited considerable antitumor activity against three tested cell lines. Conclusion: C13-esterification by a cinnamoyl group dramatically improved antitumor activity, in agreement with computational predictions. This finding provides a potential substrate for next-generation lankacidin derivatives with significant antitumor activity.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Future medicinal chemistry - 14(2022), 19 vom: 11. Okt., Seite 1349-1360 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ayoub, Ahmed Taha [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.09.2022 Date Revised 27.09.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2022-0134 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345904621 |
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| 520 | |a Background: The 17-membered polyketide, lankacidin C, exhibits considerable antitumor activity as a microtubule stabilizer by binding to the paclitaxel binding site. Method: Esterification of the C-7/C-13 hydroxyl in lankacidin C was performed with acetyl, cinnamoyl and hydrocinnamoyl groups and their antitumor activity was assessed to improve the cytotoxicity of lankacidins through bioinspired computational design. Results: Compared with the cytotoxicity of parent lankacidin C against the HeLa cell line, 13-O-cinnamoyl-lankacidin C demonstrated sevenfold higher cytotoxicity. Furthermore, 7,13-di-O-cinnamoyl-lankacidin C exhibited considerable antitumor activity against three tested cell lines. Conclusion: C13-esterification by a cinnamoyl group dramatically improved antitumor activity, in agreement with computational predictions. This finding provides a potential substrate for next-generation lankacidin derivatives with significant antitumor activity | ||
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| 700 | 1 | |a Chan, Gordon |e verfasserin |4 aut | |
| 700 | 1 | |a Morita, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Arakawa, Kenji |e verfasserin |4 aut | |
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