Studies on a Dihydrotriazine and a Sulfone, Alone and in Combination, against Plasmodium berghei in Mice

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Abstract
Summary A dihydrotriazine [4,6-diamino-1-(p-chlorophenyl)-1,2-dihydro-2,2-dimethyl-s-triazine hydrochloride] and DDS (diaminodiphenylsulfone) were studied parenterally in mice against Plasmodium berghei infections, induced with parasitized blood. The dihydrotriazine and DDS were, respectively, approximately 30 and 90 times as potent as quinine hydrochloride. By use of respective lines that had been made resistant to either drug alone, a retention of activity by the heterologous drug was determined, with only a low order of cross resistance. The joint actions by the drugs were confirmed in mixtures over a wide range of ratios. A 1:1 mixture was highly effective against the parent line and against dihydrotriazine- and DDS-resistant lines. The emergence of resistance to a 1:1 mixture developed at a significantly lower rate than to either drug alone. The rationale of a mixture of the dihydrotriazine and DDS in repository form as an antimalarial is presented.