Kumar Sumit, Gendrot Mathieu, Fonta Isabelle, Mosnier Joel, Cele Nosipho, Awolade Paul, Singh Parvesh, Pradines Bruno, Kumar Vipan
Department of Chemistry, Guru Nanak Dev University, Amritsar, Pin 143005, India.
Unité Parasitologie et Entomologie, Département Microbiologie et Maladies Infectieuses, Institut de Recherche Biomédicale des Armées, Marseille 13234, France.
ACS Med Chem Lett. 2020 Nov 23;11(12):2544-2552. doi: 10.1021/acsmedchemlett.0c00536. eCollection 2020 Dec 10.
A series of amide tethered 4-aminoquinoline-naphthalimide hybrids has been synthesized to assess their in vitro antiplasmodial potential against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of . The most active and noncytotoxic compound had an IC value of 0.07 μM against W2 strain and was more active than standard antimalarial drugs, including chloroquine, desethylamodiaquine, and quinine, particularly for drug resistant malaria. The promising scaffold, when subjected to heme binding and molecular modeling studies, was identified as a possible potent inhibitor of hemozoin formation and chloroquine resistance transporter (PfCRT), respectively, and, therefore, could act as a dual function antiplasmodial.
已合成了一系列酰胺连接的4-氨基喹啉-萘二甲酰亚胺杂化物，以评估它们对氯喹敏感（3D7）和氯喹耐药（W2）疟原虫株的体外抗疟原虫潜力。活性最高且无细胞毒性的化合物对W2株的IC值为0.07 μM，比包括氯喹、去乙基阿莫地喹和奎宁在内的标准抗疟药物更具活性，尤其是对耐药疟疾。通过血红素结合和分子模拟研究，该有前景的骨架分别被确定为可能的强效疟原虫血红素形成抑制剂和氯喹抗性转运蛋白（PfCRT）抑制剂，因此可作为一种具有双重功能的抗疟原虫药物。
