Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation
| Autor: | Shraddha V. Bhadada, Amit Kumar Verma, Neelesh Maheshwari, Piyush Trivedi, Chandan Sahi, N. S. Hari Narayana Moorthy, Chandrabose Karthikeyan |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Blood Glucose Stereochemistry Tetrazoles 01 natural sciences Biochemistry Diabetes Mellitus Experimental 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship In vivo Drug Discovery Acetamides Molecule Animals Humans Binding site Enzyme Inhibitors Molecular Biology IC50 Biological evaluation chemistry.chemical_classification Protein Tyrosine Phosphatase Non-Receptor Type 1 Binding Sites 010405 organic chemistry Organic Chemistry Glucose Tolerance Test 0104 chemical sciences Amino acid Protein Structure Tertiary Rats Mice Inbred C57BL Molecular Docking Simulation 030104 developmental biology chemistry Docking (molecular) Drug Design Acetamide |
| Zdroj: | Bioorganic chemistry. 80 |
| ISSN: | 1090-2120 |
| Popis: | Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes. |
| Databáze: | OpenAIRE |
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