The potential effects of new synthetic drugs against Leishmania amazonensis and Trypanosoma cruzi.
Amidine derivatives, never used before on trypanosomatids, were tested against Leishmania amazonensis and Trypanosoma cruzi. These drugs in doses up to 500 mg/kg inoculated into Swiss mice did not show any toxic effect (Santos, 1993). The in vitro effect of N,N'-diphenyl-4-R- benzamidine was evaluated. L. amazonensis promastigotes, epimastigotes and blood forms of T. cruzi, were assayed with/without the drugs in axenic media, using pentamidine isethionate and benznidazole, as reference drugs. The results were very promising for L. amazonensis, showing that the most active compounds were the metoxy and Br-derivatives, with LD50 of 20 microM and 22 microM, respectively. In general the amidines showed lower activity against T. cruzi than L. amazonensis. The most active compounds against blood trypomastigotes were the same metoxy and Br-derivatives, but in much higher concentrations, e.g. as LD50 of 59 nM and 251 nM, respectively. All amidines had a very low activity against epimastigotes, and the only active compounds were the halogen-derivatives with LD50 = 424 nM for the Br-derivative and LD50 of 474 nM for the C1-derivative.
Canto-Cavalheiro
M M
MM
Departamento de Imunologia, Instituto Oswaldo Cruz, Brasil.
Echevarria
A
A
Araujo
C A
CA
Bravo
M F
MF
Santos
L H
LH
Jansen
A M
AM
Leon
L L
LL
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D007894:Leishmania mexicana / Q000187:drug effects* / Q000254:growth & development; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
D000981:Antiprotozoal Agents; D001550:Benzamidines; D014344:Trypanocidal Agents