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.

C ₁₉ -二萜生物碱的药理活性与其基本骨架（如乌头碱型或茄碱型）有关。此外，很少有关于二萜生物碱的化学增敏作用的研究报道。因此，本研究旨在确定番茄碱型 C ₁₉二萜生物碱的合成衍生物对过度表达 P-糖蛋白 (P-gp) 的耐多药 (MDR) 癌细胞系 KB-VIN 的化学增敏作用。delpheline 和 delcosine 的酰基衍生物对化学敏感性癌细胞系表现出中等的细胞毒性。在非细胞毒性合成类似物 ( 1 - 14)，几种衍生物通过干扰 P-gp 对三种抗癌药物（长春新碱、紫杉醇和多柔比星）的药物转运功能，有效且显着地使 MDR 细胞敏感。衍生物2、4和6对KB-VIN细胞对长春新碱的化学增敏作用比5 μM维拉帕米更有效，衍生物4和13对紫杉醇比5 μM维拉帕米更有效。其中，2尤其将 KB-VIN 细胞对长春新碱的敏感性提高了 253 倍。