Long chain capsaicin analogues synthetized by CALB-CLEAs show cytotoxicity on glioblastoma cell lines

• Published in: Applied Microbiology and Biotechnology
• Main Authors: Diaz-Vidal, Tania, Armenta-Pérez, Vicente Paúl, Rosales-Rivera, Luis Carlos, Basulto-Padilla, Georgina Cristina, Martínez-Pérez, Raúl Balam, Mateos-Díaz, Juan Carlos, Gutiérrez-Mercado, Yanet K., Canales-Aguirre, Alejandro A., Rodríguez, Jorge A.
• Format: Text
• Language: English
• Published: Springer Berlin Heidelberg 2024
• Subjects: Biotechnological Products and Process Engineering; Antarc*; Antarctica
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10786984/; http://www.ncbi.nlm.nih.gov/pubmed/38217255; https://doi.org/10.1007/s00253-023-12856-y

ABSTRACT: 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-023-12856-y.