Metabolic chiral inversion of 2-arylpropionic acid derivatives (profens)

Abstract

2-arylpropionic acid derivatives (profens) are one of the most popular anti-inflammatory, analgesic, and antipyretic drugs. They belong to a group of nonsteroidal anti-inflammatory drugs (NSAID) and exhibit metabolic chiral inversion. Enantiomers of these chiral drugs are often characterised by different pharmacological activity. It is estimated that the values of metabolic chiral inversion of (R)-ibuprofen in humans are between 35 and 70%, depending on the condition of the liver and the intake of other medicines, while (R)-flurbiprofen undergoes chiral metabolic inversion to its opposed (S) form only in small range.The described phenomenon in the case of (R)-ketoprofen is limited to a maximum of around 10%. The metabolic chiral inversion is associated with potentially important pharmacotherapeutic and toxicological consequences, and so an attempt was made to analyse this phenomenon for the most commonly used drugs from the profens group.

Biomedical Activity of Egyptian Hibiscus sabdariffa L. as Modulator of Alzheimer’s Beta-Amyloid1-42 Secretion in a Human Neuroglioma Model

“…The IC50 values for Aβ42 inhibition estimated for R-flurbiprofen was 800.4 ng/ml that is equivalent to 3276.89 nM and was consistent with what previously reported by other authors using identical human neuroglioma cell line [12]. R-flurbiprofen was chosen as a reference drug because it reduces Aβ42 levels by targeting γ-secretase without any side effects related to inhibition of cyclooxygenase (COX) as it lacks COX activity, and in humans, undergoes very limited chiral inversion to the S-enantiomer that is active against COX [24] as well as, it was suggested that the high dose regimen may significantly slow the cognitive and functional decay of mild affected patients [25]. In our study, inhibition of Aβ42 was recognized in our red calyces for both water and aqueous ethanol extracts with concentrations less than the reference drug by approximately one and half to three times.…”

A Importância Da Expansão Da Modelagem Molecular Como Técnica Para Pesquisas De Novos Farmacos

“…O objetivo estrutural da enzima e o formato e distribuição de carga no sítio receptor possibilitou o planejamento do composto protótipo. Seguidamente utilizando a técnica da simplificação molecular o sistema cis-perisoquinolínico foi trocado por um anel piperazínico, subtraindo dois centros estereogênicos, originando o medicamento indinavir representado na figura 3 (13) . Consequentemente, por meio da simplificação molecular ficou evidenciado a importância desse método para a modelagem molecular, possibilitando o planejamento estrutural do medicamento indinavir, adquirido racionalmente da protease viral do HIV.…”

“…Consequentemente, por meio da simplificação molecular ficou evidenciado a importância desse método para a modelagem molecular, possibilitando o planejamento estrutural do medicamento indinavir, adquirido racionalmente da protease viral do HIV. Desta maneira, a avaliação da capacidade de pequenas moléculas interagirem com enzimas alvo pré-selecionadas estabelece a importância da modelagem molecular do fármaco em questão (13) .…”

Simultaneous enantioseparation of nonsteroidal anti-inflammatory drugs by a one-dimensional liquid chromatography technique using a dynamically coated chiral porous silicon pillar array column

“…Nonsteroidal anti-inflammatory drugs (NSAIDs) play an important role in modern therapy. Since most NSAIDs are chiral and each enantiomer shows different biological and therapeutic activities, the enantioselective separation of this main drug family is important [3][4][5].…”