Molecular modeling studies and in vitro bioactivity evaluation of a set of novel 5-nitro-heterocyclic derivatives as anti-T. cruzi agents.
In this study, in vitro anti-T. cruzi activity assays of nifuroxazide (NX) analogues, such as 5-nitro-2-furfuryliden and 5-nitro-2-theniliden derivatives, were performed. A molecular modeling approach was also carried out to relate the lipophilicity potential (LP) property and biological activity data. The majority of the NX derivatives showed increased anti-T. cruzi activity in comparison to the reference drug, benznidazole (BZN). Additionally, the 5-nitro-2-furfuryliden derivatives presented better pharmacological profile than the 5-nitro-2-theniliden analogues. The LP maps and corresponding ClogP values indicate that there is an optimum lipophilicity value, which must be observed in the design of new potential anti-T. cruzi agents.
Paula
Fávero Reisdorfer
FR
Departmento de Tecnologia Bioquímico-Farmacêutica, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Avenida Lineu Prestes, 580, Bloco 16, São Paulo, 05508-900, SP, Brazil.
Jorge
Salomão Dória
SD
de Almeida
Leonardo Viana
LV
Pasqualoto
Kerly Fernanda Mesquita
KF
Tavares
Leoberto Costa
LC
D000818:Animals; D062385:Hydroxybenzoates / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009581:Nitrofurans / Q000737:chemistry / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
D062385:Hydroxybenzoates; D009581:Nitrofurans; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C013150:nifuroxazide; C009999:benzonidazole