Novel 3-nitrotriazole-based amides and carbinols as bifunctional anti-Chagasic agents.
View/ Open
Volume
58
Pagination
1307 - 1319 (13)
Publisher
Publisher URL
DOI
10.1021/jm5015742
Journal
Journal of Medicinal Chemistry
Issue
ISSN
0022-2623
Metadata
Show full item recordAbstract
3-Nitro-1H-1,2,4-triazole-based amides with a linear, rigid core and 3-nitrotriazole-based fluconazole analogs 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.