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Bioactivity inspired C 19 -diterpenoid alkaloids for overcoming multidrug-resistant cancer.
- Source :
-
Journal of natural medicines [J Nat Med] 2022 Sep; Vol. 76 (4), pp. 796-802. Date of Electronic Publication: 2022 May 25. - Publication Year :
- 2022
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Abstract
- The pharmacological activities of C <subscript>19</subscript> -diterpenoid alkaloids are related to their basic skeletons (e.g., aconitine-type or lycoctonine-type). Also, few studies have been reported on the chemosensitizing effects of diterpenoid alkaloids. Consequently, this study was aimed at determining the chemosensitizing effects of synthetic derivatives of lycoctonine-type C <subscript>19</subscript> -diterpenoid alkaloids on a P-glycoprotein (P-gp)-overexpressing multidrug-resistant (MDR) cancer cell line KB-VIN. The acyl-derivatives of delpheline and delcosine showed moderate cytotoxicity against chemosensitive cancer cell lines. Among non-cytotoxic synthetic analogs (1-14), several derivatives effectively and significantly sensitized MDR cells by interfering with the drug transport function of P-gp to three anticancer drugs, vincristine, paclitaxel, and doxorubicin. The chemosensitizing effect of derivatives 2, 4, and 6 on KB-VIN cells against vincristine were more potent than 5 μM verapamil, and derivatives 4 and 13 were more effective than 5 μM verapamil for paclitaxel. Among them, 2 in particular increased the sensitivity of KB-VIN cells to vincristine by 253-fold.<br /> (© 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)
Details
- Language :
- English
- ISSN :
- 1861-0293
- Volume :
- 76
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of natural medicines
- Publication Type :
- Academic Journal
- Accession number :
- 35614289
- Full Text :
- https://doi.org/10.1007/s11418-022-01629-y