Heise Niels V, Csuk René, Mueller Thomas
Organic Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes Str. 2, 06120 Halle (Saale), Germany.
Hematology/Oncology, Medical Faculty, University Clinic for Internal Medicine IV, Martin-Luther University Halle-Wittenberg, Ernst Grube Str. 40, 06120 Halle (Saale), Germany.
Molecules. 2025 Aug 25;30(17):3488. doi: 10.3390/molecules30173488.
Capsaicin, the major pungent alkaloid in species, has been reported to exhibit cytotoxic activity through various mechanisms. In this study, capsaicin and 37 structurally related vanillylamide and ester analogs were synthesized and evaluated for cytotoxic activity and tumor cell/non-tumor cell selectivity in vitro and compared with a () extract. Seven analogs with superior potency and selectivity compared to capsaicin were identified. Notably, vanillylamides with a C-C chain exhibited IC values five-fold lower than capsaicin (15-84 µM), with selectivity indices up to 35. The extract obtained from the dried chili fruit, known to hold capsaicin as its primary component, however, exhibited significantly lower cytotoxic activity against tumor cells than pure capsaicin. These data demonstrate that even minor modifications to the acyl chain (as exemplified for the nonivamide analogs) can enhance the cytotoxicity and selectivity of these derivatives and that isolated compounds are able to offer even greater efficacy than whole-fruit extracts.
辣椒素是该物种中的主要辛辣生物碱，据报道它可通过多种机制表现出细胞毒性活性。在本研究中，合成了辣椒素及37种结构相关的香草酰胺和酯类似物，并对其体外细胞毒性活性和肿瘤细胞/非肿瘤细胞选择性进行了评估，并与一种（）提取物进行了比较。鉴定出了七种与辣椒素相比具有更高效力和选择性的类似物。值得注意的是，具有C-C链的香草酰胺的IC值比辣椒素低五倍（15-84μM），选择性指数高达35。然而，从干辣椒果实中获得的提取物，已知其主要成分是辣椒素，但其对肿瘤细胞的细胞毒性活性明显低于纯辣椒素。这些数据表明，即使对酰基链进行微小修饰（如壬酸香草酰胺类似物所示）也可以增强这些衍生物的细胞毒性和选择性，并且分离出的化合物比全果提取物具有更高的疗效。
