School of Chemistry and Materials Science, Hubei Engineering University, Hubei, PR China.
WuXi AppTec (Wuhan), Hubei, PR China.
Eur J Med Chem. 2017 Oct 20;139:22-47. doi: 10.1016/j.ejmech.2017.07.061. Epub 2017 Jul 27.
Malaria, in particular infection with P. falciparum (the most lethal of the human malaria parasite species, responsible for nearly one million deaths every year), is one of the most devastating and common infectious disease throughout the world. Beginning with quinine, quinoline containing compounds have long been used in clinical treatment of malaria and remained the mainstays of chemotherapy against malaria. The emergence of P. falciparum strains resistant to almost all antimalarials prompted medicinal chemists and biologists to study their effective replacement with an alternative mechanism of action and new molecules. Combination with variety of quinolines and other active moieties may increase the antiplasmodial and antimalarial activities and reduce the side effects. Thus, hybridization is a very attractive strategy to develop novel antimalarials. This review aims to summarize the recent advances towards the discovery of antiplasmodial and antimalarial hybrids including quinoline skeleton to provide an insight for rational designs of more active and less toxic quinoline hybrids antimalarials.
疟疾，特别是感染恶性疟原虫（最致命的人类疟原虫物种，每年导致近 100 万人死亡），是全世界最具破坏性和最常见的传染病之一。从奎宁开始，含喹啉的化合物长期以来一直被用于疟疾的临床治疗，并且仍然是抗疟疾化疗的主要药物。几乎所有抗疟药物都对恶性疟原虫产生抗药性，这促使药物化学家与生物学家研究用具有替代作用机制与新分子的药物来取代它们。与多种喹啉类药物和其他活性部分结合可能会提高抗疟原虫活性和抗疟活性，同时降低副作用。因此，杂交是开发新型抗疟药物的一种极具吸引力的策略。本综述旨在总结近年来发现的抗疟原虫和抗疟药物杂种的最新进展，包括喹啉骨架，为设计更有效、毒性更低的喹啉杂种抗疟药物提供参考。
