Laboratory of Pharmaceutical Analysis, Faculty of Medicine and Pharmacy, Research Institute for Health Sciences and Technology, University of Mons - UMONS, Place du Parc 20, 7000, Mons, Belgium.
Laboratory for Chemistry of Novel Materials, Faculty of Sciences, Research Institute for Biosciences and Research Institute for Materials, University of Mons - UMONS, Place du Parc 20, 7000, Mons, Belgium.
Int J Parasitol Drugs Drug Resist. 2022 Dec;20:97-107. doi: 10.1016/j.ijpddr.2022.10.001. Epub 2022 Oct 14.
Malaria remains to date one of the most devastating parasitic diseases worldwide. The fight against this disease is rendered more difficult by the emergence and spread of drug-resistant strains. The need for new therapeutic candidates is now greater than ever. In this study, we investigated the antiplasmodial potential of toad venoms. The wide array of bioactive compounds present in Bufonidae venoms has allowed researchers to consider many potential therapeutic applications, especially for cancers and infectious diseases. We focused on small molecules, namely bufadienolides, found in the venom of Rhinella marina (L.). The developed bio-guided fractionation process includes a four solvent-system extraction followed by fractionation using flash chromatography. Sub-fractions were obtained through preparative TLC. All samples were characterized using chromatographic and spectrometric techniques and then underwent testing on in vitro Plasmodium falciparum cultures. Two strains were considered: 3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant). This strategy highlighted a promising activity for one compound named resibufogenin. With IC values of (29 ± 8) μg/mL and (23 ± 1) μg/mL for 3D7 and W2 respectively, this makes it an interesting candidate for further investigation. A molecular modelling approach proposed a potential binding mode of resibufogenin to Plasmodium falciparum adenine-triphosphate 4 pump as antimalarial drug target.
疟疾仍然是全球最具破坏性的寄生虫病之一。抗药性疟原虫株的出现和传播使这种疾病的防治变得更加困难。现在比以往任何时候都更需要新的治疗候选药物。在这项研究中，我们研究了蟾蜍毒液的抗疟原虫潜力。Bufonidae 毒液中存在的广泛生物活性化合物使研究人员考虑了许多潜在的治疗应用，特别是癌症和传染病。我们专注于小分子量的化合物，即 Rhinella marina（L.）毒液中的蟾蜍毒苷。开发的生物导向分级分离过程包括四溶剂系统提取，然后使用快速色谱法进行分级。通过制备型 TLC 获得亚级分。所有样品均采用色谱和光谱技术进行表征，然后在体外疟原虫培养物中进行测试。考虑了两种菌株：3D7（氯喹敏感）和 W2（氯喹耐药）。这种策略突出了一种名为 resibufogenin 的化合物具有有前途的活性。对于 3D7 和 W2，其 IC 值分别为（29 ± 8）μg/mL 和（23 ± 1）μg/mL，这使其成为进一步研究的有趣候选药物。分子建模方法提出了 resibufogenin 作为抗疟药物靶标与疟原虫腺嘌呤三磷酸 4 泵的潜在结合模式。
