Physiologically relevant fluorescent assay for identification of 17β-hydroxysteroid dehydrogenase type 10 inhibitors.

Mitochondrial enzyme 17β-hydroxysteroid dehydrogenase type 10 (HSD10) is a potential molecular target for treatment of mitochondrial-related disorders such as Alzheimer's disease (AD). Its over-expression in AD brains is one of the critical factors disturbing the homeostasis of neuroprotective steroids and exacerbating amyloid beta (Aβ)-mediated mitochondrial toxicity and neuronal stress. This study was focused on revalidation of the most potent HSD10 inhibitors derived from benzothiazolyl urea scaffold using fluorescent-based enzymatic assay with physiologically relevant substrates of 17β-oestradiol and allopregnanolone.

Development of submicromolar 17β-HSD10 inhibitors and their in vitro and in vivo evaluation.

17β-hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a multifunctional mitochondrial enzyme and putative drug target for the treatment of various pathologies including Alzheimer's disease or some types of hormone-dependent cancer. In this study, a series of new benzothiazolylurea-based inhibitors were developed based on the structure-activity relationship (SAR) study of previously published compounds and predictions of their physico-chemical properties. This led to the identification of several submicromolar inhibitors (IC ∼0.

Structure Elucidation and Cholinesterase Inhibition Activity of Two New Minor Amaryllidaceae Alkaloids.

Two new minor Amaryllidaceae alkaloids were isolated from × cv. Ferrari and cv. Carlton.

Pyridinium-2-carbaldoximes with quinolinium carboxamide moiety are simultaneous reactivators of acetylcholinesterase and butyrylcholinesterase inhibited by nerve agent surrogates.

The pyridinium-2-carbaldoximes with quinolinium carboxamide moiety were designed and synthesised as cholinesterase reactivators. The prepared compounds showed intermediate-to-high inhibition of both cholinesterases when compared to standard oximes. Their reactivation ability was evaluated on human recombinant acetylcholinesterase (AChE) and human recombinant butyrylcholinesterase (BChE) inhibited by nerve agent surrogates (NIMP, NEMP, and NEDPA) or paraoxon.

RNase T1 Refolding Assay for Determining Mitochondrial Cyclophilin D Activity: A Novel Method Applicable in Drug Research and Discovery.

Human cyclophilin D is a mitochondrial peptidyl-prolyl isomerase that plays a role in regulating the opening of the mitochondrial permeability transition pore. It is considered a viable and promising molecular target for the treatment of diseases for which disease development is associated with pore opening, e.g.

Synthesis of β-d-galactopyranoside-Presenting Glycoclusters, Investigation of Their Interactions with Lectin A (PA-IL) and Evaluation of Their Anti-Adhesion Potential.

is an opportunistic human pathogen associated with cystic fibrosis. This bacterium produces, among other virulence factors, a soluble d-galactose-specific lectin PA-IL (LecA). PA-IL plays an important role in the adhesion to the host cells and is also cytotoxic.

Investigation of the Binding Affinity of a Broad Array of l-Fucosides with Six Fucose-Specific Lectins of Bacterial and Fungal Origin.

Series of multivalent α-l-fucoside containing glycoclusters and variously decorated l-fucosides were synthesized to find potential inhibitors of fucose-specific lectins and study the structure-binding affinity relationships. Tri- and tetravalent fucoclusters were built using copper-mediated azide-alkyne click chemistry. Series of fucoside monomers and dimers were synthesized using various methods, namely glycosylation, an azide-alkyne click reaction, photoinduced thiol-en addition, and sulfation.