Gupta Nikita, Kumar Kewal, Raj Raghu, Kumar Vipan
Department of Chemistry, Guru Nanak Dev University Amritsar-143005 India
Department of Chemistry, Maharaja Ranjit Singh Punjab Technical University Dabwali Road Bathinda India.
RSC Med Chem. 2025 Jul 16. doi: 10.1039/d5md00425j.
A series of hydrazinyl-oxoacetamide linked 4-aminoquinoline-phthalimides were synthesized and assayed for their anti-plasmodial activities against the chloroquine-resistant W2 strain of . The synthesized compounds exhibited activity in the low nanomolar range with eight compounds being more active than the standard drug, chloroquine (CQ). Structure-activity relationship studies indicated the dependence of anti-plasmodial activity on the length of the alkyl chain used as a spacer with two of the most promising compounds of the series exhibiting an IC value of 0.037 μM. Inhibition of hemozoin formation proved to be the primary mechanism of action of the most promising compound of the series with superior binding affinity toward heme compared to CQ.
合成了一系列肼基-氧代乙酰胺连接的4-氨基喹啉-邻苯二甲酰亚胺，并测定了它们对氯喹抗性W2株的抗疟活性。合成的化合物在低纳摩尔范围内表现出活性，其中有8种化合物比标准药物氯喹（CQ）更具活性。构效关系研究表明，抗疟活性取决于用作间隔基的烷基链的长度，该系列中最有前景的两种化合物的IC值为0.037μM。与CQ相比，该系列中最有前景的化合物对血红素具有更高的结合亲和力，抑制疟原虫血红素形成被证明是其主要作用机制。
