Departamento de Saúde, Laboratório de Bioprospecção Vegetal, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil.
Departamento de Saúde, Laboratório de Modelagem Molecular, Universidade Estadual de Feira de Santana, Feira de Santana, Bahia, Brazil.
J Biomol Struct Dyn. 2023;41(22):13383-13403. doi: 10.1080/07391102.2023.2173295. Epub 2023 Feb 6.
is found in the Brazilian semiarid region. This specie is little chemically and biologically studied. spp. have different metabolites, especially coumarins. Studies indicate that coumarins have antimalarial potential, denoting the importance of researching new active compounds from plants, since the resistance of strains to conventional therapy has increased. The present study aimed to evaluate the antiplasmodial activity of auraptene and poligalen against a chloroquine-resistant strain of . Coumarins were isolated from by open column chromatography and identified by Nuclear Magnetic Resonance Spectroscopy. A cytotoxicity assay was carried out using MTT test, and the antiplasmodial activity was evaluated using the W2 strain. The antiplasmodial activity results found were IC=0.171 ± 0.016 for auraptene and 0.164 ± 0.012 for poligalen; the selectivity indexes were 78.71 and 609.76, respectively. Inverse virtual screening in the BRAMMT database by OCTOPUS 1.2 was applied to coumarins to find potential targets and showed higher affinity energy of auraptene for purine nucleoside phosphorylase (PfPNP) and of poligalen for dihydroorotate dehydrogenase (PfDHODH). Molecular Dynamics studies (MD and MM-GBSA) approach were applied to calculate binding energies against selected targets and showed that all coumarins were stable at the binding site during simulations. Furthermore, energies were favorable for complexation. This is the first report of auraptene in species and of antiplasmodial activity of auraptene and poligalen. studies indicated that the mechanism of action of coumarins is the inhibition of PfPNP and PfDHODH.Communicated by Ramaswamy H. Sarma.
在巴西半干旱地区发现了。该种在化学和生物学方面的研究较少。 spp. 具有不同的代谢物，特别是香豆素。研究表明香豆素有抗疟潜力，这表明研究植物中新的活性化合物的重要性，因为 株对抗传统疗法的耐药性已经增加。本研究旨在评估奥瑞他汀和聚甘醇对氯喹耐药株 的抗疟活性。香豆素通过开放柱色谱法从 中分离出来，并通过核磁共振波谱法鉴定。使用 MTT 试验进行细胞毒性测定，并用 W2 株评估 抗疟活性。发现的抗疟活性结果为奥瑞他汀的 IC=0.171 ± 0.016，聚甘醇的 IC=0.164 ± 0.012；选择性指数分别为 78.71 和 609.76。通过 OCTOPUS 1.2 在 BRAMMT 数据库中进行反向虚拟筛选，以寻找潜在的 靶标，并显示奥瑞他汀对嘌呤核苷磷酸化酶（PfPNP）和聚甘醇对二氢乳清酸脱氢酶（PfDHODH）的亲和力能量更高。应用分子动力学研究（MD 和 MM-GBSA）方法计算针对选定 靶标的结合能，并表明在模拟过程中所有香豆素在结合部位均稳定。此外，能量有利于络合。这是首次报道奥瑞他汀在 种属中的存在以及奥瑞他汀和聚甘醇的抗疟活性。 研究表明，香豆素的作用机制是抑制 PfPNP 和 PfDHODH。由 Ramaswamy H. Sarma 传达。
