The rational design of novel 5-amino-2-oxindole derivatives with antiglaucomic activity.

Compounds with a 2-oxindole scaffold play an important role in organic synthesis and especially in the synthesis of bioactive organic compounds, therefore, the development of new methods for modifying this scaffold is a very interesting and urgent task. In the framework of this study, we have created a rational approach to the synthesis of 5-amino-substituted derivatives of 2-oxindole. The approach is characterized by good total yield and a small number of steps.

Microwave-Assisted Synthesis of 3-Hydroxy-2-oxindoles and Pilot Evaluation of Their Antiglaucomic Activity.

Glaucoma is a widespread neurodegenerative disease for which increased intraocular pressure (IOP) is a primary modifiable risk factor. Recently, we have observed that compounds with oxindole scaffolds are involved in the regulation of intraocular pressure and therefore have potential antiglaucomic activity. In this article, we present an efficient method for obtaining novel 2-oxindole derivatives via microwave-assisted (MW) decarboxylative condensation of substituted isatins with malonic and cyanoacetic acids.

3-Arylidene-2-oxindoles as Potent NRH:Quinone Oxidoreductase 2 Inhibitors.

The enzyme NRH:quinone oxidoreductase 2 (NQO2) plays an important role in the pathogenesis of various diseases such as neurodegenerative disorders, malaria, glaucoma, COVID-19 and cancer. NQO2 expression is known to be increased in some cancer cell lines. Since 3-arylidene-2-oxindoles are widely used in the design of new anticancer drugs, such as kinase inhibitors, it was interesting to study whether such structures have additional activity towards NQO2.

Synthesis of New 2,3-Dihydroindole Derivatives and Evaluation of Their Melatonin Receptor Binding Affinity.

2,3-Dihydroindoles are promising agents for the synthesis of new compounds with neuroprotective and antioxidant properties. Usually, these compounds are obtained by direct reduction of the corresponding indoles containing acceptor groups in the indole ring for its activation. In this work, we propose a synthetic strategy to obtain new 2,3-dihydroindole derivatives from the corresponding polyfunctional 2-oxindoles.

Synthetic Design and Biological Evaluation of New p53-MDM2 Interaction Inhibitors Based on Imidazoline Core.

The use of p53-MDM2 inhibitors is a prospective strategy in anti-cancer therapy for tumors expressing wild type p53 protein. In this study, we have applied a simple approach of two-step synthesis of imidazoline-based alkoxyaryl compounds, which are able to efficiently inhibit p53-MDM2 protein-protein interactions, promote accumulation of p53 and p53-inducible proteins in various cancer cell lines. Compounds and cause significant upregulation of p53 and p53-inducible proteins in five human cancer cell lines, one of which possesses overexpression of MDM2.

Towards multi-target antidiabetic agents: In vitro and in vivo evaluation of 3,5-disubstituted indolin-2-one derivatives as novel α-glucosidase inhibitors.

Type 2 diabetes mellitus is a chronic progressive disease that usually requires polypharmacological treatment approaches. Previously we have described a series of 2-oxindole derivatives as GSK3β inhibitors with in vivo antihyperglycemic activity. α-Glucosidase is another antidiabetic target that prevents postprandial hyperglycemia and corresponding hyperinsulinemic response.

2,4,5-Tris(alkoxyaryl)imidazoline derivatives as potent scaffold for novel p53-MDM2 interaction inhibitors: Design, synthesis, and biological evaluation.

Imidazoline-based small molecule inhibitors of p53-MDM2 interaction intended for the treatment of p53 wild-type tumors are the promising structures for design of anticancer drugs. Based on fragment approach we have investigated a key role of substituents in cis-imidazoline core for biological activity of nutlin family compounds. Although the necessity of the substituents in the phenyl rings of cis-imidazoline has been shown, there are no studies in which the replacements of a halogen by other substituents have been investigated.

Synthesis and biological evaluation of 3-substituted 2-oxindole derivatives as new glycogen synthase kinase 3β inhibitors.

Glycogen synthase kinase 3β (GSK-3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. Inhibition of GSK-3β activity has become an attractive approach for treatment of diabetes and cancer. We report the discovery of novel GSK-3β inhibitors of 3-arylidene-2-oxindole scaffold with promising activity.

Synthesis and cytotoxicity of novel simplified eleutherobin analogues as potential antitumour agents.

Mixed simplified structures containing the paclitaxel and eleutherobin pharmacophore moieties were analyzed using molecular docking techniques and synthesized based on adamantane and 8-oxabicyclo[3.2.1]octane scaffolds.

Synthesis of novel МТ3 receptor ligands via an unusual Knoevenagel condensation.

New 5-acetamido-substituted melatonin derivatives were efficiently synthesized in excellent yields via Knoevenagel condensation. The relative binding affinity of new synthesized compounds to MT3 receptor was tested via enzymatic assays and the X-ray structures of the most potent compounds were determined in complex with MT3.