THE ANTIMALARIAL ACTIVITY OF DICHLOROPHENYLTRIAZINE AND OTHER HALOGEN SUBSTITUTED DERIVATIVES

Chlorophenyltriazine is the active metabolite of chloroguanide in human body as well as in animals.In our previous study it was found that chlorophenyltriazine was highly active against P.gallinaceum.The present study was to estimate the antimalarial activity of dichlorophenyltriazine(2:4 Diamino-l(3:4-dichlorophenyl)-6:6 dimethyl-1:6 dihydro-1:3:5-(triazine)and some other halogen substituted derivatives,such as iodophenyltriazine(2:4 Diamino-1-p-iodophenyl-6:6 dimcthyl-1:6 dihydro-1:3:5 triazine),bromophenyltriazine(2:4 Diamino-1-p-bromophenyl-6:6 dimethyl-1:6 dihydro-1:3:5 triazine)and fluorophenyl-triazine((2:4 Diamino-1-p-fluorophenyl-6:6 dimethyl-1:6 dihydro-1:3:5 triazine). All the compounds examined exhibited marked effect against P.gallinaceum in chicks.Their action not only reflected on the decrease in number of plasmodia,hut also the morphological changes of the parasites.They were powerful schizontocide by attacking every stage of schizonts,although less effective on gametocytes.In addition,the toxicity of these drugs in mice by oral administration was very low. Among the series of phenyltriazine compounds,dichlorophenyltriazine was the strongest antimalarial.However,iodophenyltriazine was more effective than all other monohalogen homologues,including chlorophenyltriazine.It is anticipated that diiodo-substitution in positions 3 and 4 of the benzine ring may yield a compound more potent than dichlorophenyltriazine. Pretreatment with dichlorophenyltriazine apparently suppressed the erythrocytic development of the parasites,since in the majority of chicks no parasites observed in their peripheral blood.Nevertheless,it seemed too early to conclude that the drug had causal prophylactic effect.When dichlorophenyltriazine was repeatedly used for three successive course of therapy,no drug resistance was produced in P.gallinaceum in chicks. Since more effective derivatives are now available,it seems advantageous to abandon the use of the parent substance and employ the new synthetic drugs.