In silico and in vitro assessment of anti-Trypanosoma cruzi efficacy, genotoxicity and pharmacokinetics of pentasubstituted pyrrolic Atorvastatin-aminoquinoline hybrid compounds.

Atorvastatin (AVA) is a third-generation statin with several pleiotropic effects, considered the last synthetic pharmaceutical blockbuster. Recently, our group described the effects of AVA on DNA damage prevention and against Trypanosoma cruzi infection. In this study, our aim was to evaluate the efficacy, safety, and in silico pharmacokinetic profile of four hybrids of aminoquinolines with AVA 4a-d against T.

Phenotypic Evaluation of Nucleoside Analogues against Infection: In Vitro and In Vivo Approaches.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is a serious public health problem. Current treatment is restricted to two drugs, benznidazole and nifurtimox, displaying serious efficacy and safety drawbacks.

In Vitro Phenotypic Activity and In Silico Analysis of Natural Products from Brazilian Biodiversity on .

Chagas disease (CD) affects more than 6 million people worldwide. The available treatment is far from ideal, creating a demand for new alternative therapies. Botanical diversity provides a wide range of novel potential therapeutic scaffolds.

Combination With Tomatidine Improves the Potency of Posaconazole Against .

Azoles such as posaconazole (Posa) are highly potent against . However, when tested in chronic Chagas disease patients, a high rate of relapse after Posa treatment was observed. It appears that inhibition of cytochrome CYP51, the target of azoles, does not deliver sterile cure in monotherapy.

Efficacy of Novel Pyrazolone Phosphodiesterase Inhibitors in Experimental Mouse Models of Trypanosoma cruzi.

Pyrazolones are heterocyclic compounds with interesting biological properties. Some derivatives inhibit phosphodiesterases (PDEs) and thereby increase the cellular concentration of cyclic AMP (cAMP), which plays a vital role in the control of metabolism in eukaryotic cells, including the protozoan , the etiological agent of Chagas disease (CD), a major neglected tropical disease. phenotypic screening identified a 4-bromophenyl-dihydropyrazole dimer as an anti- hit and 17 novel pyrazolone analogues with variations on the phenyl ring were investigated in a panel of phenotypic laboratory models.