Structure-activity study of pentamidine analogues as antiprotozoal agents.
J Med Chem
; 52(7): 2016-35, 2009 Apr 09.
Article
in En
| MEDLINE
| ID: mdl-19267462
ABSTRACT
Diamidine 1 (pentamidine) and 65 analogues (2-66) have been tested for in vitro antiprotozoal activities against Trypanosoma brucei rhodesiense, Plasmodium falciparum, and Leishmania donovani, and for cytotoxicity against mammalian cells. Dications 32, 64, and 66 exhibited antitrypanosomal potencies equal or greater than melarsoprol (IC(50) = 4 nM). Nine congeners (2-4, 12, 27, 30, and 64-66) were more active against P. falciparum than artemisinin (IC(50) = 6 nM). Eight compounds (12, 32, 33, 44, 59, 62, 64, and 66) exhibited equal or better antileishmanial activities than 1 (IC(50) = 1.8 microM). Several congeners were more active than 1 in vivo, curing at least 2/4 infected animals in the acute mouse model of trypanosomiasis. The diimidazoline 66 was the most promising compound in the series, showing excellent in vitro activities and high selectivities against T. b. rhodesiense, P. falciparum, and L. donovani combined with high antitrypanosomal efficacy in vivo.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pentamidine
/
Trypanocidal Agents
/
Cadaverine
/
Imidazoles
/
Antimalarials
Limits:
Animals
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
2009
Document type:
Article
Affiliation country:
Estados Unidos