Synthesis and Evaluation of Antitumor and Anti-Angiogenesis Activity of Pyrone- or Pyridone-Embedded Analogs of Cortistatin A
Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/4/179 |
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| Summary: | Simplified analogs of cortistatin A were synthesized and biologically evaluated to develop novel antitumor substances that target angiogenesis. To analyze the effect of substituents at positions corresponding to C-2 and/or C-4 of the A-ring, various pyrone- or pyridone-embedded analogs were designed and synthesized. Among the prepared analogs, the pyridone analog <b>19</b> bearing a methyl group at C-2 and a hydroxyl group at C-4 showed potent and selective growth inhibitory activity against human umbilical vein endothelial cells (HUVECs, IC<sub>50</sub> = 0.001 µM, selective index over that against human epidermoid carcinoma KB3-1 cells = 6400), exceeding those of natural products. The analog <b>19</b> of oral administration exhibited excellent in vivo antitumor activity in mice subcutaneously inoculated with sarcoma S180 cells. |
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| ISSN: | 1660-3397 |