In vitro anti-trypanosomal potential of kaurane and pimarane semi-synthetic derivatives

Abstract

As part of the search for anti-trypanosomal agents, this work presents the production of sixteen derivatives. All of them were obtained from two natural diterpenes, one with kaurane skeleton (ent-kaurenoic acid) and other with a pimarane skeleton (ent-pimaradienoic acid). Then, the eighteen compounds were assayed against epimastigote form of Trypanosoma cruzi, with the derivatives showing increase of activity in relation to their precursors. Moreover, the most active derivative presented an IC₅₀ <12.5 µM (estimated 0.8 µM), lower than Benznidazole (IC₅₀ = 9.8 µM), used as control. The esterification of acid diterpenes showed to be an interesting way in the search for anti-trypanosomal agents.

Graphical Abstract

Keywords:

• Anti-chagasic activity
• pimarane diterpenes
• kaurane diterpenes
• structural modification
• Trypanosoma cruzi

Acknowledgements

The authors are grateful to the Coordination for the Improvement of Higher Education Personnel (CAPES) – Finance Code 001, the National Council for Scientific and Technological Development (CNPq) – grant number: 308348/2018-4, and the São Paulo Research Foundation (FAPESP) – grant number: 2009/0949-1.

Disclosure statement

No potential conflict of interest was reported by the authors.