The absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventional antimalarial drugs result in a worrisome scenario making the search for new drugs a priority. In the present study, the activities of nine neolignan derivatives were evaluated as follows: (i) against blood forms of chloroquine-resistant Plasmodium falciparum (clone W2), using the tritiated hypoxanthine incorporation and anti-HRPII assays; (ii) for cytotoxic activity against cultured human hepatoma cells (HepG2); and (iii) for intermolecular interaction with the P. falciparum cysteine protease of falcipain-2 (F2) by molecular docking. The neolignan derivatives 9 and 10 showed activity against the blood form of the chloroquine-resistant P. falciparum clone W2 and were not cytotoxic against cultured human hepatoma cells. A molecular docking study of these two neolignans with FP2 revealed several intermolecular interactions that should guide the design of future analogs.

中文翻译：

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新型新木脂素衍生物的合成，体外抗疟活性和对接研究。

由于缺乏有效的抗疟疾疫苗以及与控制蚊媒有关的困难，化学疗法已成为抗击疟疾的主要控制手段。然而，寄生虫对常规抗疟疾药物的耐药性的出现和扩散导致令人担忧的情况，使得寻找新药成为当务之急。在本研究中，对九种新木脂素衍生物的活性进行了如下评估：（i）使用tri化的次黄嘌呤掺入法和抗HRPII法检测抗氯喹抗性恶性疟原虫（克隆W2）的血型；（ii）针对培养的人肝癌细胞（HepG2）的细胞毒活性；（iii）通过分子对接与恶性疟原虫-2（F2）的恶性疟原虫半胱氨酸蛋白酶进行分子间相互作用。新木脂素衍生物9和10显示出抗氯喹抗性恶性疟原虫克隆W2的血型的活性，并且对培养的人肝癌细胞没有细胞毒性。对这两个新木脂素与FP2的分子对接研究表明，分子间的相互作用应指导未来类似物的设计。