DNA binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity.
A new antitrypanosomal hit compound that cures an acute (STIB 900) mouse model of Trypanosoma brucei rhodesiense trypanosomiasis is described. This bis(2-aminoimidazolinium) dicationic compound proved to be an excellent DNA minor groove binder, suggesting a possible mechanism for its trypanocidal activity. From these studies, the 4,4'-diaminodiphenylamine skeleton emerged as a good scaffold for antitrypanosomal drugs.
Dardonville
Christophe
C
Instituto de Química Médica, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain. dardonville@iqm.csic.es
Barrett
Michael P
MP
Brun
Reto
R
Kaiser
Marcel
M
Tanious
Farial
F
Wilson
W David
WD
D000818:Animals; D004247:DNA / Q000737:chemistry*; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D033703:Nucleoside Transport Proteins / Q000235:genetics; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000401:mortality
D006146:Guanidines; D048288:Imidazolines; D033703:Nucleoside Transport Proteins; C486446:P2 transporter, Trypanosoma brucei; D014344:Trypanocidal Agents; D004247:DNA