Musonda Chitalu C, Yardley Vanessa, de Souza Renata C Carvalho, Ncokazi Kanyile, Egan Timothy J, Chibale Kelly
Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
Org Biomol Chem. 2008 Dec 7;6(23):4446-51. doi: 10.1039/b813007h. Epub 2008 Oct 24.
A novel series of 4-aminoquinoline-containing 2-imidazolines were synthesized via a one-pot 3-component condensation reaction of amine, aldehyde and isocyanoacetate. The products were obtained in high yield as well as purity and were evaluated directly against two strains of Plasmodium falciparum and Trypanosoma brucei. Compound was the most active across all parasites with ED(50) = 3.3 nM against a chloroquine (CQ)-sensitive 3D7 strain, ED(50) = 33 nM against a CQ-resistant K1 strain and ED(50) = 70 nM against T. brucei. Several compounds were able to inhibit formation of beta-haematin in vitro, suggesting haemozoin formation in the malaria parasite as a possible target. On the other hand, evaluation against a human KB cell line revealed that the compounds were generally non-cytotoxic to the host cells.
通过胺、醛和异氰基乙酸酯的一锅三组分缩合反应，合成了一系列新型含4-氨基喹啉的2-咪唑啉。产物以高产率和高纯度获得，并直接针对两种恶性疟原虫和布氏锥虫菌株进行了评估。化合物在所有寄生虫中活性最高，对氯喹（CQ）敏感的3D7菌株的半数有效剂量（ED50）= 3.3 nM，对CQ耐药的K1菌株的ED50 = 33 nM，对布氏锥虫的ED50 = 70 nM。几种化合物能够在体外抑制β-血红素的形成，这表明疟原虫中疟色素的形成可能是一个靶点。另一方面，对人KB细胞系的评估表明，这些化合物通常对宿主细胞无细胞毒性。
