Cheruku Srinivasa R, Maiti Souvik, Dorn Arnulf, Scorneaux Bernard, Bhattacharjee Apurba K, Ellis William Y, Vennerstrom Jonathan L
College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA.
J Med Chem. 2003 Jul 3;46(14):3166-9. doi: 10.1021/jm030038x.
Unlike diprotic chloroquine (CQ), its two 4-aminoquinoline carbon isosteres (1, 2) are monoprotic at physiological pH. Compared to CQ, hematin binding affinity of 1 decreased 6.4-fold, and there was no measurable binding for 2. Although 1 was a weak inhibitor of hemozoin formation, neither isostere inhibited P. falciparum in vitro. Evidently, the CQ-hematin interaction is largely a function of its pyridine substructure, but inhibition of hemozoin formation and parasite growth depends on its 4-aminopyridine substructure.
与二质子化的氯喹（CQ）不同，其两种4-氨基喹啉碳电子等排体（1、2）在生理pH条件下为单质子化。与CQ相比，1与血红素的结合亲和力降低了6.4倍，而2则没有可测量的结合。尽管1是疟原虫血红蛋白形成的弱抑制剂，但两种电子等排体在体外均未抑制恶性疟原虫。显然，CQ与血红素的相互作用在很大程度上取决于其吡啶亚结构，但疟原虫血红蛋白形成和寄生虫生长的抑制作用则取决于其4-氨基吡啶亚结构。
