title: An abietane diterpene from Salvia cuspidata and some new derivatives are active against Trypanosoma cruzi.
abstract: 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 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.
authors.affiliation: Laboratorio de Biología y Fisiología Celular, 'Dr. Francisco Bertini', Instituto de Histología y Embriología-CONICET, Facultad de Ciencias Médicas, UNCuyo, Mendoza, Argentina.
authors.forename: E S
authors.initials: ES
authors.lastname: Lozano
authors.affiliation: Laboratorio de Biología y Fisiología Celular, 'Dr. Francisco Bertini', Instituto de Histología y Embriología-CONICET, Facultad de Ciencias Médicas, UNCuyo, Mendoza, Argentina.
authors.forename: R M
authors.initials: RM
authors.lastname: Spina
authors.affiliation: INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, UNSL, San Luis, Argentina.
authors.forename: C E
authors.initials: CE
authors.lastname: Tonn
authors.affiliation: Laboratorio de Biología y Fisiología Celular, 'Dr. Francisco Bertini', Instituto de Histología y Embriología-CONICET, Facultad de Ciencias Médicas, UNCuyo, Mendoza, Argentina. Electronic address: msosa@fcm.uncu.edu.ar.
authors.forename: M A
authors.initials: MA
authors.lastname: Sosa
authors.affiliation: INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, UNSL, San Luis, Argentina.
authors.forename: D A
authors.initials: DA
authors.lastname: Cifuente
mesh_terms: D045784:Abietanes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D027544:Salvia / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*; D014709:Vero Cells
chemical_list: D045784:Abietanes; D010936:Plant Extracts; D014344:Trypanocidal Agents
keywords: Diterpenes; Natural products; Salvia cuspidata; Trypanosoma cruzi