An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi

ESTEBAN S. LOZANO; RENATA SPINA; CARLOS E. TONN; MIGUEL A. SOSA; DIEGO A. CIFUENTE

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 vol. 25 p. 5481 - 5484

0960-894X

The Plant Kingdom is an excellent source for obtaining natural compounds with antiprotozoal activity. In the present work, we studied the effect of the diterpene 12-hydroxy-11,14-diketo-6,8,12-abietatrien-19,20-olide (HABTO) obtained from the aerial parts of Salvia cuspidata on Trypanosoma cruzi epimastigotes. This compound was found to inhibit parasite growth even at low concentrations (IC50 5 µg/mL) and with low toxicity on mammalian cells. In addition, this diterpene induced an intense vacuolization within the parasites. In order to obtain analogues with greater lipophilicity, chemical modifications on the the enol moiety were carried out to obtain the acetyl (AABTO), the sylil (SABTO) and the allyl (ALLABTO) derivatives. We observed that the SABTO was the most effective one on the parasites, and the effect could be attributed to a greater lipophilicity of this compound. Taking into account these data we conclude that the increase of lipophilicity by chemical modifications is an adequate strategy for improving the trypanocidal activity of this kind abietane diterpenes.