The present research aimed to evaluate in silico the pharmacodynamics, pharmacokinetics and toxicity of syringic and ursolic acids isolated from Actinidia delicious and to analyze the mechanism that underlies its performance in cholesterol reduction comparing them with the drug simvastatin. The PreADME online server was used to evaluate the pharmacokinetic and toxicological profile through the molecular structure-activity and the AutodockVina software to study the pharmacodynamics and pharmacological potential of molecular interactions. The ADME data obtained for the syringic and ursolic acids were similar to those for simvastatin, in the analysis of the molecular docking it was evidenced that the results were approximate between the tested molecules, however the ursolic acid overlapped with greater interaction stability with the biological target when compared to simvastatin. It was possible to observe from the results that the evaluated compounds are qualified for subsequent in vitro and in vivo tests for a more in-depth study of their anti-hyperlipemic action.
Isopropyl gallate (IPG) is a polyphenol obtained from alterations in the gallic acid molecule via acid catalysis with previously reported leishmanicidal and trypanocidal activities. The present study aims to evaluate in silico binding activity towards some targets for antileishmanial chemotherapy against Leishmania major species, and ADMET parameters for IPG, as well as in vitro antileishmanial and cytotoxic effects. Molecular docking was performed using AutoDockVina and BIOVIA Discovery Studio software, whereas in silico analysis used SwissADME, PreADMET and admetSAR software. In vitro antileishmanial activity on promastigotes and amastigotes of Leishmania major, cytotoxicity and macrophages activation were assessed. IPG exhibited affinity for pteridine reductase (PTR1; −8.2 kcal/mol) and oligopeptidase B (OPB; −8.0 kcal/mol) enzymes. ADMET assays demonstrated good lipophilicity, oral bioavailability, and skin permeability, as well as non-mutagenic, non-carcinogenic properties and low risk of cardiac toxicity for IPG. Moreover, IPG inhibited the in vitro growth of promastigotes (IC50 = 90.813 µM), presented significant activity against amastigotes (IC50 = 13.45 μM), promoted low cytotoxicity in macrophages (CC50 = 1260 μM), and increased phagocytic capacity. These results suggest IPG is more selectively toxic to the parasite than to mammalian cells. IPG demonstrated acceptable in silico pharmacokinetics parameters, and reduced infection and infectivity in parasitized macrophages, possibly involving macrophage activation pathways and inhibition of leishmania enzymes.
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