New Potential Antimalarials:Antirelapse Compound, CDRI 80/53

Abstract

Sporozoite-induced infections in rhesus monkey for useful for establishing models for causal prophylactic and anti-relapse screening test systems. Ex¬perimental transmission of sporozoite- induced P, cynomolgi B infection through rhesus monkey has been maintained successfully since 1982 by serial cyclic passage. using .A. stephensi as vector. The radical curative dose of primaquine in this model had been found to be I mg (base)/kg x 7 day(by oral route), which gives 100% curative rate. Chloroquine used as companion blood schizontocide with primaquine was curative at 3 mg (base)/kg x 7 days. A short 3-day treatment schedule with primaquine as reference drug had been standardized for evaluation of causal prophylactic activity of potential antimalarials, A dose of 1.78 mg/kg primaquine (base) x 3 days (days - 1,0 and +1) had been found to be consistently curative. Sporozoite-induced P. cynomulgi B rhesus infection is the unique model developed at CDRI for large scale screening of new anti-relapse/causal prophylactic agents. A new 8-aminoquinoline derivative (CDRI 80/53), (N1-(3-acetyl-4-5¬dihydro-2-furanyl)-N4-(6-methoxy 8-quinoliny1)l, 4- pentanediamine). synthesized at CDRI, Lucknow, showed causal prophylactic activity at 3.16 mg,lkg x 3 doses (on days -1, 0 and+1 ) against sporozoite-induced P. cynomolgi B infection in rhesus monkeys. This new compound also exerts anti-relapse (radical curative) activity at 1 mg/kg x 7 days.