Biotecnología Industrial, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, CIATEJ, 45019, Zapopan, Mexico.
Departamento de Ingeniería Química, CUCEI, Universidad de Guadalajara, 44430, Guadalajara, Mexico.
Appl Microbiol Biotechnol. 2024 Dec;108(1):106. doi: 10.1007/s00253-023-12856-y. Epub 2024 Jan 12.
Glioblastoma is one of the most lethal tumors, displaying striking cellular heterogeneity and drug resistance. The prognosis of patients suffering from glioblastoma after 5 years is only 5%. In the present work, capsaicin analogues bearing modifications on the acyl chain with long-chain fatty acids showed promising anti-tumoral activity by its cytotoxicity on U-87 and U-138 glioblastoma multiforme cells. The capsaicin analogues were enzymatically synthetized with cross-linked enzyme aggregates of lipase B from Candida antarctica (CALB). The catalytic performance of recombinant CALB-CLEAs was compared to their immobilized form on a hydrophobic support. After 72 h of reaction, the synthesis of capsaicin analogues from linoleic acid, docosahexaenoic acid, and punicic acid achieved a maximum conversion of 69.7, 8.3 and 30.3% with CALB-CLEAs, respectively. Similar values were obtained with commercial CALB, with conversion yields of 58.3, 24.2 and 22% for capsaicin analogues from linoleic acid, DHA and punicic acid, respectively. Olvanil and dohevanil had a significant cytotoxic effect on both U-87 and U-138 glioblastoma cells. Irrespective of the immobilization form, CALB is an efficient biocatalyst for the synthesis of anti-tumoral capsaicin derivatives. KEY POINTS: • This is the first report concerning the enzymatic synthesis of capsaicin analogues from docosahexaenoic acid and punicic acid with CALB-CLEAs. • The viability U-87 and U-138 glioblastoma cells was significantly affected after incubation with olvanil and dohevanil. • Capsaicin analogues from fatty acids obtained by CALB-CLEAs are promising candidates for therapeutic use as cytotoxic agents in glioblastoma cancer cells.
胶质母细胞瘤是最致命的肿瘤之一，表现出明显的细胞异质性和耐药性。 5 年后患有胶质母细胞瘤的患者的预后仅为 5%。 在本工作中，带有酰基链修饰的辣椒素类似物用长链脂肪酸表现出有希望的抗肿瘤活性，对 U-87 和 U-138 多形性成胶质细胞瘤细胞具有细胞毒性。 用南极假丝酵母脂肪酶 B 的交联酶聚集体（CALB）酶法合成了辣椒素类似物。 比较了重组 CALB-CLEAs 的催化性能与其固定在疏水载体上的形式。 反应 72 小时后，用 CALB-CLEAs 分别从亚油酸、二十二碳六烯酸和 punica 酸合成辣椒素类似物的转化率达到了 69.7%、8.3%和 30.3%。 用商业 CALB 获得了类似的值，亚油酸、二十二碳六烯酸和 punica 酸的转化率分别为 58.3%、24.2%和 22%。 Olvanil 和 dohevanil 对 U-87 和 U-138 胶质母细胞瘤细胞均具有显著的细胞毒性作用。 无论固定化形式如何，CALB 都是合成抗肿瘤辣椒素衍生物的有效生物催化剂。 关键点： • 这是首次用 CALB-CLEAs 从二十二碳六烯酸和 punica 酸酶法合成辣椒素类似物的报道。 • 与 olvanil 和 dohevanil 孵育后，U-87 和 U-138 胶质母细胞瘤细胞的活力明显受到影响。 • 用 CALB-CLEAs 从脂肪酸获得的辣椒素类似物是作为胶质母细胞瘤癌细胞细胞毒性剂治疗用途的有希望的候选物。
