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.