[Study on structure-activity relationships of hemolytic toxicity of primaquine derivatives]

Primaquine (PQ) and it's 13 derivatives were tested in an in vitro assay system incorporated with liver-microsomal metabolism for their hemolytic toxicity, and 6 putative metabolites of PQ were also assayed in the same system without microsomal metabolism. The results showed that in the 13 derivatives, the hemolytic toxicity of 4-methyl PQ derivatives was lower than that of PQ while 5-trifluoroacetyl PQ derivatives exhibited similar hemolytic potential to PQ. Various modification of the 8-amino side chain of PQ has no significant effect on the hemolytic toxicity of PQ. In the 6 putative metabolites of PQ, 5-OH PQ and 5,6-OH PQ were the most potent hemolytic toxidants which could produce similar level of methemoglobin formation at concentrations several orders of magnitude less than that of PQ, while the hemolytic toxicity of 6-OH PQ, AQD and AQL was also higher than that of PQ itself. MAQ was the only one which exhibited no hemolytic toxicity.