Synthesis and Evaluation of Antimalarial Properties of Novel 4-Aminoquinoline Hybrid Compounds
Synthesis and Evaluation of Antimalarial Properties of Novel 4-Aminoquinoline Hybrid Compounds
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DOI：
10.1111/cbdd.12335
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发表时间：
2014-10-01
影响因子：
3
通讯作者：
Poulsen, Sally-Ann
中科院分区：
文献类型：
--
作者：
Fisher, Gillian M.;Tanpure, Rajendra P.;Poulsen, Sally-Ann
药效团杂交最近被用于寻找抗疟疾的先导化合物。这种方法用化学方法将两种各自具有抗疟疾活性且理想情况下具有不同作用模式的药效团连接成一个单一的杂交分子，目的是改善治疗特性。本文报道了新型7-氯-4-氨基喹啉/伯胺杂化化合物的合成。氯化的4-氨基喹啉支架是氯喹的核心结构，氯喹是一种已建立的抗疟药物，而主要的磺胺官能团在许多临床使用的药物中已被证明具有疗效和安全性，最近显示出一些抗疟活性。测定了杂合物对氯喹敏感（3D7）和耐氯喹（Dd2）恶性疟原虫的抑菌活性。虽然与氯喹相比，杂交化合物的抗疟活性较低，但它们显示出许多有趣的结构-活性关系（SAR）趋势，包括克服氯喹耐药性的潜力。
Pharmacophore hybridization has recently been employed in the search for antimalarial lead compounds. This approach chemically links two pharmacophores, each with their own antimalarial activity and ideally with different modes of action, into a single hybrid molecule with the goal to improve therapeutic properties. In this paper, we report the synthesis of novel 7-chloro-4-aminoquinoline/primary sulfonamide hybrid compounds. The chlorinated 4-aminoquinoline scaffold is the core structure of chloroquine, an established antimalarial drug, while the primary sulfonamide functional group has a proven track record of efficacy and safety in many clinically used drugs and was recently shown to exhibit some antimalarial activity. The activity of the hybrid compounds was determined against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum strains. While the hybrid compounds had lower antimalarial activity when compared to chloroquine, they demonstrated a number of interesting structure-activity relationship (SAR) trends including the potential to overcome the resistance profile of chloroquine.