1. Bioactivity inspired C 19 -diterpenoid alkaloids for overcoming multidrug-resistant cancer.
- Author
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Wada K, Goto M, Ohkoshi E, Lee KH, and Yamashita H
- Subjects
- Drug Resistance, Multiple, Drug Resistance, Neoplasm, Humans, Paclitaxel pharmacology, Verapamil pharmacology, Vincristine pharmacology, Alkaloids pharmacology, Diterpenes pharmacology, Neoplasms
- Abstract
The pharmacological activities of C
19 -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 C19 -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., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)- Published
- 2022
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