Dicationic DNA-targeted antiprotozoal agents: naphthalene replacement of benzimidazole.
Bioorg Med Chem
; 14(22): 7434-45, 2006 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-16889966
ABSTRACT
A series of naphthalene analogues of highly active benzimidazole diamidines were synthesized using sequential Stille and Suzuki coupling reactions for preparation of the bis-nitrile intermediates. All of the diamidines showed strong DNA affinities as judged by high DeltaTm values with poly(dA-dT). The dicationic compounds were quite active in vitro versus Trypanosoma brucei rhodesiense (T. b. r.) exhibiting IC50 values ranging from 4 to 98 nM. These compounds were also active versus Plasmodium falciparum (P. f.) giving IC50 values ranging from 4 to 33 nM. Two of the compounds showed good activity in vivo in the STIB900 model for acute African trypanosomiasis; one gave 3/4 cures and the other gave 4/4 cures on ip dosage of 20 mg/kg for 4 days. The amidoxime prodrugs of the naphthalene analogues were essentially ineffective.
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Bases de datos:
MEDLINE
Asunto principal:
Bencimidazoles
/
ADN
/
Naftalenos
/
Antiprotozoarios
Límite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos