Activity of natural and synthetic polygodial derivatives against Trypanosoma cruzi amastigotes, trypomastigotes and epimastigotes

Abstract

Our laboratories have been investigating biological effects of a sesquiterpenoid polygodial and its natural and synthetic analogues. Herein, we report the evaluation of these compounds against the three forms of Trypanosoma cruzi, amastigotes, trypomastigotes and epimastigotes. Although polygodial was found to be poorly active, its natural congener epipolygodial and synthetic Wittig-derived analogues showed low micromolar potency against all three forms of the parasite. Synthetic α,β-unsaturated phosphonate 9 compared favorably with clinically approved drugs benznidazole and nifurtimox, and was effective against trypomastigotes, toward which benznidazole showed no activity.

Keywords:

• Trypanosoma cruzi
• polygodial
• anti-parasitic
• phosphonate
• Wittig derivatives
• terpenes

Acknowledgement

The authors thank Dr. R.L. Tarleton for his generous gift of the CL tdTomato (DTU TcVI) Trypanosoma cruzi parasites.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This project was supported by grants from the US National Institute of General Medical Sciences (Grant P20GM103451), NMT Presidential Research Support and Australian Government for a Research Training Program Scholarship.