Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents
The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent c...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/13/3052 |
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| author | Eirik J. Solum Sandra Liekens Trond Vidar Hansen |
| author_facet | Eirik J. Solum Sandra Liekens Trond Vidar Hansen |
| author_sort | Eirik J. Solum |
| collection | DOAJ |
| description | The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC<sub>50</sub> values < 10µM. The most interesting <b>10l</b> analog exhibited an IC<sub>50</sub> value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent <b>10h</b> compound reduced the activity of CDK8 to 35%. |
| first_indexed | 2024-03-10T18:41:57Z |
| format | Article |
| id | doaj.art-d65c09b35fdb444eb517cfac133b1f3c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:41:57Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-d65c09b35fdb444eb517cfac133b1f3c2023-11-20T05:48:00ZengMDPI AGMolecules1420-30492020-07-012513305210.3390/molecules25133052Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer AgentsEirik J. Solum0Sandra Liekens1Trond Vidar Hansen2Faculty of Health Sciences, Nord University, 7801 Namsos, NorwayLaboratory of Virology and Chemotherapy, Rega Institute for Medical Research, Department of Microbiology and Immunology, KU Leuven, Herestraat 49, Postbus 1043, B-3000 Leuven, BelgiumSchool of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, NorwayThe synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC<sub>50</sub> values < 10µM. The most interesting <b>10l</b> analog exhibited an IC<sub>50</sub> value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent <b>10h</b> compound reduced the activity of CDK8 to 35%.https://www.mdpi.com/1420-3049/25/13/3052anti-canceranti-leukemiaCDK8 inhibitionsteroidscortistatin A |
| spellingShingle | Eirik J. Solum Sandra Liekens Trond Vidar Hansen Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents Molecules anti-cancer anti-leukemia CDK8 inhibition steroids cortistatin A |
| title | Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents |
| title_full | Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents |
| title_fullStr | Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents |
| title_full_unstemmed | Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents |
| title_short | Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents |
| title_sort | synthesis and biological evaluation of analogs of didehydroepiandrosterone as potential new anticancer agents |
| topic | anti-cancer anti-leukemia CDK8 inhibition steroids cortistatin A |
| url | https://www.mdpi.com/1420-3049/25/13/3052 |
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