Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Avenida Brasil 4365, Manguinhos, Rio de Janeiro 210360-040, Brazil.
Laboratório de Tecnologia para Biodiversidade em Saúde/LDFito, Instituto de Tecnologia em Fármacos (Farmanguinhos), Fundação Oswaldo Cruz (FIOCRUZ), Avenida Brasil 4365, Manguinhos, Rio de Janeiro 210360-040, Brazil.
Molecules. 2021 Sep 18;26(18):5676. doi: 10.3390/molecules26185676.
Chagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds. Presently, our aim was to evaluate the mammalian host toxicity and anti- activity of botanic natural products including extracts, fractions and purified compounds obtained from Brazilian flora. In this study, 36 samples of extracts and fractions and eight pure compounds obtained from seven plant species were evaluated. The fraction dichloromethane from var. (AFfPD) and the crude extract of (PTFrE) showed promising trypanosomicidal activity. AFfPD and PTFrE presented EC values 10.7 ± 2.8 μg/mL and 12.85 ± 1.52 μg/mL against intracellular forms (Tulahuen strain), respectively. Additionally, both were active upon bloodstream trypomastigotes (Y strain), exhibiting EC 2.2 ± 1.0 μg/mL and 38.8 ± 2.1 μg/mL for AFfPD and PTFrE, respectively. Importantly, AFfPD is about five-fold more potent than Benznidazole (Bz), the reference drug for CD, also reaching lower EC value (7.92 ± 2.2 μg/mL) as compared to Bz (23.3 ± 0.6 μg/mL). Besides, anti-parasitic effect of eight purified botanic substances was also investigated. Aurelianolide A and B (compounds and ) from and compound from displayed the best trypanosomicidal effect. Compounds , and showed EC of 4.6 ± 1.3 μM, 1.6 ± 0.4 μM and 8.1 ± 0.9 μM, respectively against intracellular forms. In addition, in silico analysis of these three biomolecules was performed to predict parameters of absorption, distribution, metabolism and excretion. The studied compounds presented similar ADMET profile as Bz, without presenting mutagenicity and hepatotoxicity aspects as predicted for Bz. Our findings indicate that these natural products have promising anti- effect and may represent new scaffolds for future lead optimization.
恰加斯病（CD）影响着全球超过 600 万人。现有的治疗方法远非理想，因此需要新的替代疗法。植物多样性提供了广泛的新的潜在治疗支架。目前，我们的目的是评估包括提取物、馏分和从巴西植物群中获得的纯化合物在内的植物天然产物对哺乳动物宿主的毒性和抗活性。在这项研究中，评估了来自七种植物的 36 种提取物和馏分以及 8 种纯化合物。二氯甲烷馏分（AFfPD）和 的粗提物（PTFrE）显示出有希望的杀锥虫活性。AFfPD 和 PTFrE 对细胞内形式（Tulahuen 株）的 EC 值分别为 10.7±2.8μg/mL 和 12.85±1.52μg/mL。此外，两者对血流中的锥虫（Y 株）均具有活性，AFfPD 和 PTFrE 的 EC 2.2±1.0μg/mL 和 38.8±2.1μg/mL。重要的是，AFfPD 的效力比本芴醇（Bz），即 CD 的参考药物，高出约五倍，其 EC 值也低于 Bz（7.92±2.2μg/mL）。此外，还研究了八种纯化植物物质的抗寄生虫作用。 Aurelianolide A 和 B（化合物 和 ）来自 和来自 的化合物 显示出最好的杀锥虫作用。化合物 、 和 对细胞内形式的 EC 值分别为 4.6±1.3μM、1.6±0.4μM 和 8.1±0.9μM。此外，对这三种生物分子进行了计算机模拟分析，以预测吸收、分布、代谢和排泄的参数。研究的化合物表现出与 Bz 相似的 ADMET 特征，没有表现出如预测的 Bz 那样的致突变性和肝毒性。我们的研究结果表明，这些天然产物具有有前途的抗活性，可能代表未来的优化先导化合物的新支架。
