Biocatalytic Synthesis of Terpene Esters and their Biological Activity in Human Glioma Cells

Abstract

Background: Gliomas are highly malignant brain tumours with high resistance to chemotherapy. Therefore, investigations of new therapeutic molecules with high anti-glioma activity are of great importance.

Objectives: In this work, biocatalytic esterification of terpene alcohols with proven anti-cancer activity was performed to enhance their potency to induce cell death in human glioblastoma multiforme T98G and anaplastic astrocytoma MOGGCCM cell lines in vitro.

Methods and results: We used primary terpene alcohols and carboxylic acids with a length of two to nine carbon atoms. The structure of the alcohols had an influence on the esterification efficiency, which decreased in the following order: monocyclic > linear > bicyclic. Terpene alcohols and their esters only induced apoptotic cell death, which is highly desirable from a therapeutic point of view, but did not induce autophagy and necrosis. The esterification of perillyl alcohol with butyric acid caused a 4-fold increase in cell death induction in the T98G line. Citronellol valerate, caprylate, and pelargonate and myrtenol butyrate, caprylate and pelargonate also showed higher activity than their alcohol precursors.

Conclusion: We have herein shown that esterification of natural alcohols by biocatalysis can be used for improving the activity of other compounds investigated for their anti-glioma activity.

Keywords: Terpene esters; apoptosis; biocatalysis; biological activity; esterification; glioblastoma.