伯喹有机酸盐的合成及其对疟疾根治作用的实验观察

作者等根据某些药物制成复盐后,可增加疗效或减低毒性,从而用酸碱反应法合成了各种伯喹的有机酸盐。经对鸡疟Plasmodium gallinaceum及鼠疟P.yoelii初筛,以伯喹3,5-二碘水杨酸盐(M 74018)疗效较好,进一步试验证明M 74018对食蟹猴疟原虫(P.cynomolgi)的组织期、对根治子孢子引起的感染以及对孢子增殖作用都有良好的作用,这些作用都比磷酸伯喹稍佳。共毒性则与磷酸伯喹相当。

SYNTHESIS OF ORGANIC SALTS OF PRIMAQUINE AND EXPERIMENTAL OBSERVATIONS ON THEIR RADICAL CURE ACTIVITY AGAINST MALARIA

According to the fact that the effectiveness of certain drugs can be enhanced or their toxicity reduced by preparing their organic salts, the authors have synthesized a variety of organic salts of primaquine and carried out experimental observations on their radical cure activity against malaria. These salts were prepared by treating an ethanol or ether solution of primaquine base with various organic acids in the same solvent. The primaquine salts obtained were as follows: Primaquine salicylate (1),benzoate (2), 3,5-diiodosalicylate (3), gallate (4),p-iodobenzoate (5),2,4-dichlorobenzoate (6), barbiturate (7),5-sulfosalicylate(8),syringate (9),2-furoate (10),3,5-dinitrobenzoate (11),5-nitrosalicylate (12),palmitate (13),β-(furyl-2-)-acrylate (14), anisate (15), L-glutamate (16),myristate (17) and primaquine tyrosine salt (18).Experimental results showed that the primaquine salts 3 and 7 were effective against Plasmodium gallinaceum in chicks and salts 13～17 were effective against P.yoelii in mice. Among these, primaquine 3,5-diiodosalicylate (3),coded M74018,was subjected to further experimental observations. The results indicated that M 74018 was superior to primaquine phosphate in its effectiveness against the tissue stage, and the sporozoite-induced infection of P. cynomolgi in monkeys and its suppression on the sporogony in Anopheles stephensi. Its toxicity, however, was similar to that of primaquine phosphate.