1921
Volume 57, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645
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Abstract

Abstract

The growth inhibitory effect of 3-deazaneplanocin A (cNpcA) was tested against some pathogenic members of the family of American Trypanosomatidae. Under our culture conditions, cNpcA displayed a strongly and uniformly leishmanistatic effect on all 23 American ( and ) strains in the study (mean dose producing 50% inhibition compared with control parasite growth [ID] = 96 ng/ml, 0.32 µM), but showed no inhibition against the several and strains tested with concentrations up to 10,000 ng/ml. This compound also induced a substantial expansion of the intracellular pools of both S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), as well as a significant diminution of the AdoMet:AdoHcy ratio. Strong AdoHcy hydrolase activity was detected in American promastigotes. At at a dose of 200 ng/ml, cNpcA inhibited S-adenosyl-L-H-methylmethionine and -thymidine incorporation by promastigotes after four days incubation in the presence of the drug. At a dose of 100 ng/ml, cNpcA eliminated approximately 56% of the and from infected human macrophages, compared with simultaneously cultivated controls. Two schedules of 10 consecutive intraperitoneal injections of cNpcA, with doses ranging from 0.5 to 1.5 mg/kg/day, significantly reduced development of cutaneous leishmanial infection produced in inbred BALB/c mice by inoculation, although a few parasites remained at the inoculation site.

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/content/journals/10.4269/ajtmh.1997.57.407
1997-10-01
2017-11-24
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