Construction of 1,3,4-oxadiazolines bearing CF-quaternary centers amino-assisted [3 + 2] cycloadditions.

An amino-assisted [3 + 2] cycloaddition strategy of nitrile imines with -aminotrifluoroacetophenones has been explored, thus providing functionalized 1,3,4-oxadiazolines bearing CF-quaternary centers in good to excellent yields in the presence of KCO under mild conditions. The amino groups located at the -position of trifluoroacetophenone might play a crucial role in the present cyclization. The MTT assay shows that the 1,3,4-oxadiazoline derivatives could be potential candidates for the treatment of head and neck cancers.

Design and synthesis of novel quinazolin-4(1H)-one derivatives as potent and selective inhibitors targeting AKR1B1.

Inhibition of aldose reductase (AKR1B1) is a promising option for the treatment of diabetic complications. However, most of the developed small molecule inhibitors lack selectivity or suffer from low bioactivity. To address this limitation, a novel series of quinazolin-4(1H)-one derivatives as potent and selective inhibitors of AKR1B1 were designed and synthesized.

Identification of 9H-purin-6-amine derivatives as novel aldose reductase inhibitors for the treatment of diabetic complications.

A series of 9H-purin-6-amine derivatives as aldose reductase (ALR) inhibitors were designed and synthesized. Most of these derivatives, having a C6-substituted benzylamine side chain and N9 carboxylic acid on the core structure, were found to be potent and selective ALR inhibitors, with submicromolar IC values against ALR2. Particularly, compound 4e was the most active with an IC value of 0.

Novel 3,4-dihydroquinolin-2(1H)-one derivatives as dual inhibitor targeting AKR1B1/ROS for treatment of diabetic complications: Design, synthesis and biological evaluation.

AKR1B1 (Aldose reductase) has been used as therapeutic intervention target for treatment of diabetic complications over 50 years, and more recently for inflammation and cancer. However, most developed small molecule inhibitors have the defect of low bioactivity. To address this limitation, novel series of 3,4-dihydroquinolin-2(1H)-one derivatives as dual inhibitor targeting AKR1B1/ROS (Reactive Oxygen Species) were designed and synthesized.

GSH responsive nanomedicines self-assembled from small molecule prodrug alleviate the toxicity of cardiac glycosides as potent cancer drugs.

Cardiac glycosides (CGs) have been used to treat cancer for hundreds of years. However, the narrow therapeutic window and system toxicity have hindered their wide clinical applications. Herein, the small molecule prodrug strategy and nanotechnology were integrated into one drug delivery system with enhanced therapeutic effect.

Identification of quinoxalin-2(1)-one derivatives as a novel class of multifunctional aldose reductase inhibitors.

Targeting aldose reductase and oxidative stress with quinoxalin-2(1)-one derivatives having a 1-hydroxypyrazole head as the bioisosteric replacement of carboxylic acid. Aldose reductase inhibition, selectivity and antioxidant potency of all the synthesized compounds were evaluated, and binding modes were studied by molecular docking. Most of the derivatives showed potent and selective aldose reductase inhibition, and among them was the most active (IC = 0.

Novel 2-phenoxypyrido[3,2-]pyrazin-3(4)-one derivatives as potent and selective aldose reductase inhibitors with antioxidant activity.

To develop multifunctional aldose reductase (AKR1B1) inhibitors for anti-diabetic complications, a novel series of 2-phenoxypyrido[3,2-]pyrazin-3(4)-one derivatives were designed and synthesised. Most of the derivatives were found to be potent and selective against AKR1B1, and 2-(7-chloro-2-(3,5-dihydroxyphenoxy)-3-oxopyrido[3,2-]pyrazin-4(3)-yl) acetic acid () was the most active with an IC value of 0.023 µM.

Synthesis and structure-activity relationship studies of phenolic hydroxyl derivatives based on quinoxalinone as aldose reductase inhibitors with antioxidant activity.

To enhance aldose reductase (ALR2) inhibition and add antioxidant ability, phenolic hydroxyl was introduced both to the quinoxalinone core and C3 side chain, resulting in a series of derivatives as ALR2 inhibitors. Biological activity tests suggested that most of the derivatives were potent and selective inhibitors with IC values ranging from 0.059 to 6.

A series of pyrido[2,3-b]pyrazin-3(4H)-one derivatives as aldose reductase inhibitors with antioxidant activity.

A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0.009 μM.

Topical composition for treating diabetic cataracts: a patent evaluation (WO2015026380A1).

Diabetes mellitus is a major threat to global public health that requires long-term medical attention. In view of the potentially devastating effects of diabetes on ocular health, it highlights the urgent need of therapeutic drugs for the prevention and treatment of the diabetic complications. The patent described in this evaluation (WO2015026380A1) claimed a topical composition for treating diabetic cataracts both in animals and human beings.

Phenolic 4-hydroxy and 3,5-dihydroxy derivatives of 3-phenoxyquinoxalin-2(1H)-one as potent aldose reductase inhibitors with antioxidant activity.

A group of novel quinoxalinone derivatives (4a-h) were prepared and investigated for their inhibitory activity against ALR2 and antioxidant activity. Most of them were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.019 to 0.