bulaquine and Malaria

A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.

Topics: Antiprotozoal Agents; Cell Line, Tumor; Dose-Response Relationship, Drug; HEK293 Cells; Humans; Liver; Malaria; Molecular Structure; Parasitic Sensitivity Tests; Plasmodium falciparum; Quinine; Structure-Activity Relationship

The gametocytocidal action of a new enamine analogue of primaquine, elubaquine (compound CDRI 80/53, bulaquine), has been evaluated against Plasmodium cynomolgi B in rhesus monkeys. Colony bred Anopheles stephensi mosquitoes were fed on gametocyte carrying rhesus monkeys prior to and at varying intervals after oral administration of a single dose of elubaquine at doses ranging between 0.63 and 5.00 mg/kg. Complete loss of oocyst development and mosquito infectivity was observed within 24 h after administering a single 1.25 mg/kg dose, while higher dose of 3.75 mg/kg inhibited oocyst development within 5 h, indicating gametocytocidal action of the compound. Elubaquine did not show any action against developing oocysts in the vector.

Topics: Animals; Anopheles; Antimalarials; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Insect Vectors; Macaca mulatta; Malaria; Male; Plasmodium cynomolgi; Primaquine

A new 8-aminoquinoline derivative, N1-(3-acetyl-4-5-dihydro-2 furanyl)-N4-(6-methoxy-8-quinolinyl)1,4-pentanediamine, synthesized at CDRI, Lucknow, showed causal prophylactic activity at 3.16 mg/kg x 3 doses (on day -1, 0 and +1) against sporozoite induced P. cynomolgi B infection in rhesus monkeys. Single dose of 10 mg/kg of this compound on day 0 also prevented establishment of patient infection. Activity of the compound was comparable to that of primaquine (with causal prophylactic activity at 1.78 mg/kg in three day test and at 10.0 mg/kg in single dose test).

Topics: Animals; Antimalarials; Macaca mulatta; Malaria; Primaquine

An analogue of primaquine, N1-(3-acetyl-4-5-dihydro-2-furanyl)-N4-(6-methoxy-8-quinolinyl) 1,4-pentanediamine, CDRI Code 80/53), has been evaluated for anti-relapse activity against sporozoite induced Plasmodium cynomolgi B infection in rhesus monkeys. The compound has shown 100% curative anti-relapse activity at 1.25 mg/kg x 7 day dose schedule, thereby giving a primaquine index of 0.8. The compound is currently under Phase-I clinical trials.

Topics: Aminoquinolines; Animals; Antimalarials; Drug Evaluation, Preclinical; Macaca mulatta; Malaria; Molecular Structure; Primaquine