Record number :
Title of article :
Dicationic biphenyl benzimidazole derivatives as antiprotozoal agents Original Research Article
Author/Authors :
Mohamed A. Ismail، نويسنده , , Reto Brun، نويسنده , , Tanja Wenzler، نويسنده , , Farial A. Tanious، نويسنده , , W. David Wilson، نويسنده , , David W. Boykin، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2004
Pages :
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Abstract :
A series of biphenyl benzimidazoles diamidines 6a–i were synthesized from their respective diamidoximes, through the bis-O-acetoxyamidoxime followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd–C. The target compounds contain hydroxy and/or methoxy substituted 1,3-phenyl groups as the central spacer between the two amidino bearing aryl groups. All of the diamidines showed strong DNA affinities as judged by high ΔTm values with poly(dA·dT)2, which varied with structure and is discussed. Seven of the nine new diamidines gave in vitro IC50 values of approximately 30 nM or less versus Trypanosoma brucei rhodesiense (T.b.r.). Generally the diamidines were less active versus Plasmodium falciparum (P.f.), however one compound exhibited excellent activity with an IC50 value of 2.1 nM. Five of the nine diamidines exhibited excellent in vivo activity in the trypanosomal STIB900 mouse model giving 3/4 or 4/4 cures at dosage of 20 mg/kg ip and three showed similar efficacy at dosage of 10 mg/kg or lower.
Keywords :
Diamidines , Benzimidazoles , Antiprotozoal agents , 1 , Suzuki coupling , 3-Phenylene
Journal title :
Bioorganic and Medicinal Chemistry
Link To Document :