Bioactivity inspired C19-diterpenoid alkaloids for overcoming multidrug-resistant cancer.
J Nat Med
; 76(4): 796-802, 2022 Sep.
Article
in En
| MEDLINE
| ID: mdl-35614289
ABSTRACT
The pharmacological activities of C19-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diterpenes
/
Alkaloids
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
J Nat Med
Journal subject:
TERAPIAS COMPLEMENTARES
Year:
2022
Document type:
Article
Affiliation country:
Japan