Acivicin: a highly active potential chemotherapeutic agent against visceral leishmaniasis.
Acivicin, a chlorinated amino acid antibiotic, is found to be remarkably effective in killing both the vector and the host form of the parasitic protozoa, Leishmania donovani, the causative agent for visceral leishmaniasis or Kala-azar. The ED50 (50 nM) for the pathogenic amastigote form in in vitro screening system is significantly lower than the reported values for other drugs under trial. The drug irreversibly inactivates both in vitro and in vivo carbamyl phosphate synthetase II, the first enzyme of the pyrimidine biosynthetic pathway. The irreversible inactivation of this sensitive target enzyme and lack of effective reversal by glutamine makes acivicin a preferred candidate for potential chemotherapy against increasing number of Kala-azar cases that are reported to be unresponsive to pentavalent antimonials.
Mukherjee
T
T
Enzyme Division, Indian Institute of Chemical Biology, Calcutta.
Roy
K
K
Bhaduri
A
A
D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D007555:Isoxazoles / Q000627:therapeutic use*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010080:Oxazoles / Q000627:therapeutic use*
D000981:Antiprotozoal Agents; D007555:Isoxazoles; D010080:Oxazoles; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing); C006303:acivicin