title: Novel 3-nitrotriazole-based amides and carbinols as bifunctional antichagasic agents.
abstract: 3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogues were synthesized as dual functioning antitrypanosomal agents. Such compounds are excellent substrates for type I nitroreductase (NTR) located in the mitochondrion of trypanosomatids and, at the same time, act as inhibitors of the sterol 14α-demethylase (T. cruzi CYP51) enzyme. Because combination treatments against parasites are often superior to monotherapy, we believe that this emerging class of bifunctional compounds may introduce a new generation of antitrypanosomal drugs. In the present work, the synthesis and in vitro and in vivo evaluation of such compounds is discussed.
authors.affiliation: NorthShore University HealthSystem , Evanston, Illinois 60201, United States.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Papadopoulou
authors.forename: William D
authors.initials: WD
authors.lastname: Bloomer
authors.forename: Galina I
authors.initials: GI
authors.lastname: Lepesheva
authors.forename: Howard S
authors.initials: HS
authors.lastname: Rosenzweig
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Benjamín
authors.initials: B
authors.lastname: Aguilera-Venegas
authors.forename: Shane R
authors.initials: SR
authors.lastname: Wilkinson
authors.forename: Eric
authors.initials: E
authors.lastname: Chatelain
authors.forename: Jean-Robert
authors.initials: JR
authors.lastname: Ioset
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D004305:Dose-Response Relationship, Drug; D000432:Methanol / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D051381:Rats; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000577:Amides; D014230:Triazoles; D014344:Trypanocidal Agents; D000432:Methanol