Synthesis, activity, metabolic stability and cell permeability of new cytosolic phospholipase A(2)alpha inhibitors with 1-indolyl-3-phenoxypropan-2-one structure

Article Biochemistry & Molecular Biology

Synthesis and pharmacokinetic properties of novel cPLA2? inhibitors with 1-(carboxyalkylpyrrolyl)-3-aryloxypropan-2-one structure br

Angelina Subeska et al.

Summary: This passage describes the potent potential of Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 as anti-inflammatory drugs, but only very low plasma concentrations could be achieved through oral administration in animal experiments. To optimize the metabolic stability, structural modifications were made but did not result in higher plasma concentrations. Cellular permeation assays revealed that these substances were good substrates for gastrointestinal efflux transporters, explaining their poor oral absorption.

BIOORGANIC & MEDICINAL CHEMISTRY (2023)

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Article Chemistry, Medicinal

Hexafluoroisopropyl Carbamates as Selective MAGL and Dual MAGL/FAAH Inhibitors: Biochemical and Physicochemical Properties

Maximilian Barth et al.

Summary: A series of hexafluoroisopropyl carbamates with indolylalkyl- and azaindolylalkyl-substituents were synthesized and tested for inhibition of the endocannabinoid degrading enzymes FAAH and MAGL. The compounds with alkyl chains incorporated into a piperidine ring showed selective MAGL inhibition, while an extension of the alkyl spacer resulted in dual FAAH/MAGL inhibition. The reactive hexafluoroisopropyl carbamate group was found to be mainly responsible for the inhibitory effect. Some derivatives showed slightly higher MAGL inhibition and improved physicochemical and biochemical properties compared to the known MAGL inhibitor ABX-1431.

CHEMMEDCHEM (2022)

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Article Medicine, Research & Experimental

Contribution of cyclooxygenase-1-dependent prostacyclin synthesis to bradykinin-induced dermal extravasation

Michael Krybus et al.

Summary: In this study, the researchers investigated the role of prostaglandins and cyclooxygenase (COX) in non-allergic angioedema. They found that COX-1-dependent prostacyclin production plays a critical role in dermal extravasation after activation of B2 receptors. Targeting prostacyclin production and/or signaling may be a suitable option for the acute treatment of non-allergic angioedema.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Review Pharmacology & Pharmacy

The design and discovery of phospholipase A2 inhibitors for the treatment of inflammatory diseases

Charikleia S. Batsika et al.

Summary: This article summarizes the development of synthetic inhibitors targeting the four major types of human PLA(2), discussing their activities, applications, and therapeutic properties. It also examines the role of PLA(2) in the pathobiology of COVID-19.

EXPERT OPINION ON DRUG DISCOVERY (2021)

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Review Biochemistry & Molecular Biology