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

• Published in: Bioorganic & medicinal chemistry letters 2015-12, Vol.25 (23), p.5481-5484
• Main Authors: Lozano, E.S., Spina, R.M., Tonn, C.E., Sosa, M.A., Cifuente, D.A.
• Format: Article
• Language: English
• Subjects: Animals; Cell Survival - drug effects; Cercopithecus aethiops; Diterpenes; Diterpenes, Abietane - chemistry; Diterpenes, Abietane - isolation & purification; Diterpenes, Abietane - pharmacology; Molecular Structure; Natural products; Plant Extracts - chemistry; Plant Extracts - pharmacology; Salvia - chemistry; Salvia cuspidata; Trypanocidal Agents - chemistry; Trypanocidal Agents - isolation & purification; Trypanocidal Agents - pharmacology; Trypanosoma cruzi; Trypanosoma cruzi - drug effects; Vero Cells
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.10.082

[Display omitted] 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 5μg/mL) and with low toxicity on mammalian cells. In addition, this diterpene induced an intense vacuolization within the parasites. In order to obtain analogs with greater lipophilicity, chemical modifications on 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.