Efficacy of novel pyrazolone phosphodiesterase inhibitors in experimental mouse models of Trypanosoma cruzi was written by Siciliano de Araujo, Julianna;da Silva, Cristiane Franca;da Gama Jaen Batista, Denise;Nefertiti, Aline;Ferreira de Almeida Fiuza, Ludmila;Fonseca-Berzal, Cristina Rosa;da Silva, Patricia Bernardino;Batista, Marcos Meuser;Sijm, Maarten;Kalejaiye, Titilola D.;de Koning, Harry P.;Maes, Louis;Sterk, Geert Jan;Leurs, Rob;de Nazare Correia Soeiro, Maria. And the article was included in Antimicrobial Agents and Chemotherapy in 2020.Recommanded Product: 1614-12-6 This article mentions the following:
Pyrazolones are heterocyclic compounds with interesting biol. properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cAMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan Trypanosoma cruzi, the etiol. agent of Chagas disease (CD), a major neglected tropical disease. In vitro phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as an anti-T. cruzi hit and 17 novel pyrazolone analogs with variations on the Ph ring were investigated in a panel of phenotypic laboratory models. Potent activity against the intracellular forms (Tulahuen and Y strains) was obtained with 50% effective concentration (EC50) values within the 0.17 to 3.3μM range. Although most were not active against bloodstream trypomastigotes, an altered morphol. and loss of infectivity were observed Pretreatment of the mammalian host cells with pyrazolones did not interfere with infection and proliferation, showing that the drug activity was not the result of changes to host cell metabolism The pyrazolone NPD-227 increased the intracellular cAMP levels and was able to sterilize T. cruzi-infected cell cultures. Thus, due to its high potency and selectivity in vitro, and its additive interaction with benznidazole (Bz), NPD-227 was next assessed in the acute mouse model. Oral dosing for 5 days of NPD-227 at 10 mg/kg + Bz at 10 mg/kg not only reduced parasitemia (>87%) but also protected against mortality (>83% survival), hence demonstrating superiority to the monotherapy schemes. These data support these pyrazolone mols. as potential novel therapeutic alternatives for Chagas disease. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Recommanded Product: 1614-12-6).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. Triazoles consist of a five-membered ring containing three nitrogen atoms and are biologically active, especially as antifungal, antimicrobial and enzyme inhibitors. Triazoles are compounds with a vast spectrum of applications, varying from materials (polymers), agricultural chemicals, pharmaceuticals, photoactive chemicals and dyes.Recommanded Product: 1614-12-6
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics