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Abstract：
Amphibians are widely known as a prolific source of bioactive metabolites. In this work, we isolated and characterized compounds with antiparasitic activity from the oocytes of the toad Rhinella alata collected in Panama. Bio-guided isolation and structural elucidation were carried out using chromatographic and spectroscopic techniques, respectively. The organic extract was subjected to solid phase extraction followed by HPLC purification of the fraction with in vitro activity against Trypanosoma cruzi trypomastigotes. Seven steroids (1-7) of the bufadienolide family were isolated, and their structures were determined using NMR and MS analyses; of these 19-formyl-dyscinobufotalin, (3) is reported as a new natural product. Compounds 1 and 3-7 resulted in a good anti-trypanosomal activity profile. Among these, 16β-hydroxyl-hellebrigenin (1) and bufalin (7) showed significant selectivity values of >5 and 2.69, respectively, while the positive control benznidazole showed a selectivity of 18.81. Furthermore, molecular docking analysis showed compounds 1, 3 and 7 interact through H-bonds with the amino acid residues GLN-19, ASP-158, HIS-159 and TRP-177 from cruzipain at the catalytic site. Given the lack of therapeutic options to treat American trypanosomiasis, this work can serve as the basis for further studies that aim for the development of bufadienolides or their derivatives as drugs against Chagas disease.
摘要：
两栖动物被广泛认为是生物活性代谢物的多产来源。在这项工作中,我们从巴拿马收集的蟾蜍Rhinellaalata的卵母细胞中分离并表征了具有抗寄生虫活性的化合物。使用色谱和光谱技术进行生物引导的分离和结构阐明，分别。对有机提取物进行固相萃取，然后对具有体外抗锥虫锥虫活性的级分进行HPLC纯化。分离出了丁非二烯醇内酯家族的七个类固醇（1-7），并使用NMR和MS分析确定它们的结构；在这些19-甲酰-dyscinobufotalin中，(3)被报导为新的天然产物。化合物1和3-7产生良好的抗锥虫活性曲线。其中,16β-羟基-冬青素（1）和bufalin（7）分别显示>5和2.69的显着选择性值，而阳性对照苯并咪唑显示出18.81的选择性。此外，分子对接分析表明，化合物1、3和7通过H键与催化位点的crazipain的氨基酸残基GLN-19，ASP-158，HIS-159和TRP-177相互作用。鉴于缺乏治疗美国锥虫病的治疗选择，这项工作可以作为进一步研究的基础，旨在开发bufadienolides或其衍生物作为对抗查加斯病的药物。
