Anti-<i>Trypanosoma cruzi</i> activity of clerodane diterpenes and their methyl ester derivatives from <i>Aquarius grandiflorus</i> (Alismataceae)

The effect of the EtOAc extract of <i>Aquarius grandiflorus</i> leaves against <i>Trypanosoma cruzi</i> (trypomastigotes) was evaluated <i>in vitro</i>. As this extract caused 100% parasite reduction (at 300 µg/mL), it was subjected to chromatographic fractionation to obtain two related diterpenes, clerodermic (<b>1</b>) and patagonic (<b>2</b>) acids. Both compounds showed antiparasitic potential against <i>T. cruzi</i> with EC₅₀ of 41.7 µM (trypo)/60.7 µM (ama) and 37.6 µM (trypo)/73.1 µM (ama), respectively. Considering that the antiparasitic activity of carboxylic acid diterpenoids may be enhanced after esterification, methylation of both compounds was performed. The EC₅₀ values for methyl esters <b>1a</b> and <b>2a</b> were determined to be 19.7 µM (trypo)/7.5 µM (ama) and 21.8 µM (trypo)/9.3 µM (ama), respectively. Based on the potency of the methyl esters, they may be future candidates for optimisation studies to design new drugs for treatment of Chagas’ disease.