Lozano E S, Spina R M, Tonn C E, Sosa M A, Cifuente D A
Laboratorio de Biología y Fisiología Celular, 'Dr. Francisco Bertini', Instituto de Histología y Embriología-CONICET, Facultad de Ciencias Médicas, UNCuyo, Mendoza, Argentina.
INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, UNSL, San Luis, Argentina.
Bioorg Med Chem Lett. 2015 Dec 1;25(23):5481-4. doi: 10.1016/j.bmcl.2015.10.082. Epub 2015 Oct 27.
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.
植物王国是获取具有抗原生动物活性天然化合物的极佳来源。在本研究中，我们研究了从鼠尾草地上部分获得的二萜类化合物12-羟基-11,14-二酮-6,8,12-枞三烯-19,20-内酯（HABTO）对克氏锥虫前鞭毛体的影响。发现该化合物即使在低浓度（IC50为5μg/mL）时也能抑制寄生虫生长，并且对哺乳动物细胞毒性较低。此外，这种二萜类化合物会导致寄生虫体内出现强烈的空泡化现象。为了获得具有更高亲脂性的类似物，对烯醇部分进行了化学修饰，得到了乙酰基（AABTO）、硅烷基（SABTO）和烯丙基（ALLABTO）衍生物。我们观察到SABTO对寄生虫最为有效，这种效果可能归因于该化合物具有更高的亲脂性。考虑到这些数据，我们得出结论，通过化学修饰提高亲脂性是提高此类枞烷二萜类化合物杀锥虫活性的一种合适策略。
