| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
We evaluated the structure-activity relationship of the compounds which were prepared in these two years and whose lead compound is 4,4'(41,4.TetramethylenedicarbonyldiamineThis(1-hexyl- pyridinium bromide). As a result, it was found that 1) substituent on pyridine ring nitroigen contributes to antimalarial activity greatly; 2) this substituent show the highest activity in the case that the number of tha alkyl chain carbone on pyridine ring nitroigen is 8; 3) when this substituent is bulky just like a benzyl or cyclohexyl group, the antimalarial activity deduced 4) the change of the carbon numbers of the linker which joines two pyridine rings from 3 to 10 did not give so large influence for the antimalarial activity. We also evaluated the compound which showed superior antimalarial activity in vitro in these two years for antimalarial activity in vivo. The 4 days suppressive test on mouse was used for the evaluation methods. As a result, ED50 value of our compound was 7.3 mg/kg in dosage of 15 mg/kg. This value showed that our compound is effective although the activity of our compound was only partial response inferior to (1/5~1/6) in chloroquine (ED50 value ; 1.3 mg/kg) which was existing medicine. However, in the case of our compound, malaria infected mise did not reach to complete recovery and survival ratio was 186%. While chloroquine have let malaria infection mise recover completely. When the duration of administration of this compound was extended, amelioration of clear macrobiotic coefficient was recognized. That is, by the extention of the duration of administration, inhibitory effect of malarial parasite was clearly recognized (less than 2%). From these results, it is thought that our compound cannot completely restrain malaria infection alone, however, combination use of our compound with existing antimalarials will reach to complete recovery of malaria infection dieses.
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