Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)
| Autor: | Janaswamy Madhusudana Rao, Puppala Muthenna, Vidadala Rama Subba Rao, Chandrasekhar Akileshwari, G. Shankaraiah, Katragadda Suresh Babu, Kothakonda Rajendra Prasad, Rotte Sateesh Chandra Kumar, Kothapalli Hari Babu, Geereddy Bhanuprakash Reddy, J. Mark Petrash, Ganji Suresh, Potharaju Ashok Yadav |
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| Rok vydání: | 2012 |
| Předmět: |
Erythrocytes
Indoles Stereochemistry Plant Roots Article Structure-Activity Relationship chemistry.chemical_compound Aldehyde Reductase Drug Discovery Humans Hypoglycemic Agents Sorbitol Structure–activity relationship Enzyme Inhibitors Piperidones Enzyme Assays Pharmacology Indole test Aldose reductase Natural product biology Plant Extracts Organic Chemistry Biological Transport General Medicine biology.organism_classification Recombinant Proteins Piper chaba Molecular Docking Simulation chemistry Drug Design Michael reaction Piper |
| Zdroj: | European Journal of Medicinal Chemistry. 57:344-361 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2012.09.014 |
| Popis: | As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells. |
| Databáze: | OpenAIRE |
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