The deficit of effective treatments for Chagas disease has led to searching for new substances with therapeutic
potential. Natural products possess a wide variety of chemical structural motifs and are thus a valuable source of
diverse lead compounds for the development of new drugs. Castanedia santamartensis is endemic to Colombia,
and local indigenous communities often use it to treat skin sores from leishmaniasis; however, its mechanism of
action against the infective form of Trypanosoma cruzi has not been determined. Thus, we performed chemical
and biological studies of two alcoholic leaf extracts of C. santamartensis to identify their active fractions and
relate them to a trypanocidal effect and evaluate their mechanism of action. Alcoholic extracts were obtained
through cold maceration at room temperature and fractionated using classical column chromatography. Both
ethanolic and methanolic extracts displayed activity against T. cruzi. Chemical studies revealed that kaurenoic
acid was the major component of one fraction of the methanolic extract and two fractions of the ethanolic extract
of C. santamartensis leaves. Moreover, caryophyllene oxide, kaurenol, taraxasterol acetate, pentadecanone, and
methyl and ethyl esters of palmitate, as well as a group of phenolic compounds, including ferulic acid, caffeic
acid, chlorogenic acid, myricetin, quercitrin, and cryptochlorogenic acid were identified in the most active
fractions. Kaurenoic acid and the most active fractions CS400 and CS402 collapsed the mitochondrial membrane
potential in trypomastigotes, demonstrating for the first time the likely mechanism against T. cruzi, probably due
to interactions with other components of the fractions.
