PDF(Pubmed)
Abstract：
Plakortinic acids C (1) and D (2), an unseparable pair of endoperoxide polyketides isolated and purified from the symbiotic association of Caribbean Sea sponges Plakortis symbiotica-Xestospongia deweerdtae, underwent in vitro evaluation for antiplasmodial activity against the malaria parasite Plasmodium berghei using a drug luminescence assay. Initial screening at 10 µM revealed 50% in vitro parasite growth inhibition. The title compounds displayed antiplasmodial activity with an EC50 of 5.3 µM toward P. berghei parasites. The lytic activity against erythrocytes was assessed through an erythrocyte cell lysis assay, which showed non-lytic activity at lower concentrations ranging from 1.95 to 3.91 µM. The antiplasmodial activity and the absence of hemolytic activity support the potential of plakortinic acids C (1) and D (2) as promising lead compounds. Moreover, drug-likeness (ADMET) properties assessed through the pkCSM server predicted high intestinal absorption, hepatic metabolism, and volume of distribution, indicating favorable pharmacokinetic profiles for oral administration. These findings suggest the potential suitability of these metabolites for further investigations of antiplasmodial activity in multiple parasitic stages in the mosquito and Plasmodium falciparum. Notably, this study represents the first report of a marine natural product exhibiting the unique 7,8-dioxatricyclo[4.2.2.02,5]dec-9-ene motif being evaluated against malaria.
摘要：
铅酸C（1）和D（2），从加勒比海海绵Plakortissymbointica-Xestospongiadeweerdtae的共生关系中分离和纯化的一对内过氧化物聚酮化合物，使用药物发光测定法对疟原虫伯氏疟原虫的抗疟药活性进行了体外评估。在10μM的初始筛选显示50％的体外寄生虫生长抑制。标题化合物对伯氏疟原虫寄生虫的EC50为5.3µM，具有抗疟原虫活性。通过红细胞裂解试验评估对红细胞的裂解活性，在1.95至3.91µM的较低浓度下显示出非裂解活性。抗疟药活性和不存在溶血活性支持了plakortinic酸C（1）和D（2）作为有前途的先导化合物的潜力。此外，通过pkCSM服务器评估的药物相似度(ADMET)特性预测的高肠道吸收，肝代谢，和分配量，表明口服给药有利的药代动力学特征。这些发现表明，这些代谢物可能适合进一步研究蚊子和恶性疟原虫在多个寄生阶段的抗疟原虫活性。值得注意的是,这项研究代表了首次报告显示独特的7,8-二氧三环[4.2.2.02,5]dec-9-ene基序的海洋天然产品正在评估其对疟疾的作用。
