Proguanil

Aromatic biguanides such as proguanil (181) have been found useful as antimalarial agents. Investigation of the metabolism of this class of drugs revealed that the active compound was in fact the triazine produced by oxidative cyclization onto the terminal alkyl group. The very rapid excretion of the active entity means that it cannot be used as such in therapy. Consequently, treatment usually consists in administration of either the metabolic precursor or, alternately, the triazine as some very insoluble salt to provide slow but continual release of drug. 

Dapsone, an aromatic sulfone, is administered in combination with a proguanil derivative. Dapsone... 

Proguanil appears to have a dual activity. Part of it is metabolized to cycloguanil, which subsequently inhibits the protozaon dihydrofolate reduc-tase/thymidylate synthase (DHFR/TS) (Fig. 4). In addition, the native form, proguanil itself, exerts a potent antimalarial activity, especially in combination with other antimalarial drugs. The target of proguanil is unknown. 

ACTs with amodiaquine, atovaquone-proguanil, chloroquine, clindamycin, doxycycline, lumefantrine,... 

Materials Required Proguanil hydrochloride 0.6 g ammoniacal cupric chloride solution (dissolve 22.5 g of copper (II) chloride in 200 ml of DW and mix with 100 ml of 13.5 M ammonia) NO. 4 sintered-glass crucible mixture of dilute solution of ammonia and DW (1 5). 

Theory Gravimetric analysis of proguanil hydrochloride involves the precipitation of the proguanil-cupric complex that results on the addition of ammoniacal cupric chloride solution to a solution of proguanil hydrochloride. The reaction can be expressed by the following equation ... 

Different antimalarials selectively kill the parasite s different developmental forms. The mechanism of action is known for some of them pyrimethamine and dapsone inhibit dihydrofolate reductase (p. 273), as does chlorguanide (proguanil) via its active metabolite. The sulfonamide sulfadoxine inhibits synthesis of dihydrofolic acid (p. 272). Chlo-roquine and quinine accumulate within the acidic vacuoles of blood schizonts and inhibit polymerization of heme, the latter substance being toxic for the schizonts. 

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