79 research outputs found
Design and evaluation of non-carboxylate 5-arylidene-2-thioxo-4-imidazolidinones as novel non-competitive inhibitors of protein tyrosine phosphatase 1B
In search for multi-target ligands as potential agents for diabetes mellitus and its complications—a structure-activity relationship study on inhibitors of aldose reductase and protein tyrosine phosphatase 1b
Diabetes mellitus (DM) is a complex disease which currently affects more than 460 million people and is one of the leading cause of death worldwide. Its development implies numerous metabolic dysfunctions and the onset of hyperglycaemia-induced chronic complications. Multiple ligands can be rationally designed for the treatment of multifactorial diseases, such as DM, with the precise aim of simultaneously controlling multiple pathogenic mechanisms related to the disease and providing a more effective and safer therapeutic treatment compared to combinations of selective drugs. Starting from our previous findings that highlighted the possibility to target both aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP1B), two enzymes strictly implicated in the development of DM and its complications, we synthesised 3-(5-arylidene-4-oxothiazolidin-3-yl)propanoic acids and analogous 2-butenoic acid derivatives, with the aim of balancing the effectiveness of dual AR/PTP1B inhibitors which we had identified as designed multiple ligands (DMLs). Out of the tested compounds, 4f exhibited well-balanced AR/PTP1B inhibitory effects at low micromolar concentrations, along with interesting insulin-sensitizing activity in murine C2C12 cell cultures. The SARs here highlighted along with their rationalization by in silico docking experiments into both target enzymes provide further insights into this class of inhibitors for their development as potential DML antidiabetic candidates
ChemInform Abstract: New 4-[(5-Arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic Acids (VII) Active as Protein Tyrosine Phosphatase Inhibitors Endowed with Insulinomimetic Effect on Mouse C2C12 Skeletal Muscle Cells.
ChemInform Abstract: Halogenated Isoniazid Derivatives. Part 4. 1-Methylideneamino-2- trifluoromethylaziridines from Isonicotinoylhydrazones and Diazomethane.
ChemInform Abstract: Halogenated Isoniazid Derivatives. Part 2. Unusual Synthesis of δ 2-1,3,4-Oxadiazoline Derivatives from Isonicotinoylhydrazones and Diazomethane.
ChemInform Abstract: Identification of 5-Arylidene-4-thiazolidinone Derivatives Endowed with Dual Activity as Aldose Reductase Inhibitors and Antioxidant Agents for the Treatment of Diabetic Complications.
Complexity in Sustainability: an Investigation of the Italian Urban System trough Self-Reflexive Neural Networks
Synthesis and Antiproliferative Evaluation of 2′-Arenesulfonyloxy-5-benzylidene-thiazolidine-2,4-diones
Synthesis and antifungal activity of novel 2-benzimidazolylimino-5-arylidene-4-thiazolidinones
Tetraplex DNA specific ligands based on the fluorenone-carboxamide scaffold
A series of fluorenone-carboxamide compounds was analyzed with regard to DNA binding properties by UV spectroscopy
and competition dialysis methods. The morpholino derivative 10 provided interesting results in terms of affinity and specificity toward the DNA G-tetraplex structures. Interactions against this target were evaluated by a comparative molecular modeling study in agreement with the experimental data, proposing a model for the rational design of new agents with potent and selective DNA tetraplex binding properties
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