914336-50-8Relevant articles and documents
Dicationic DNA-targeted antiprotozoal agents: Naphthalene replacement of benzimidazole
Chackal-Catoen, Sarah,Miao, Yi,Wilson, W. David,Wenzler, Tanja,Brun, Reto,Boykin, David W.
, p. 7434 - 7445 (2007/10/03)
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 ΔTm 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.