Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy
| العنوان: | Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy |
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| المؤلفون: | P. B. Kavi Kishor, P. V. B. S. Narayana, G. Gyananath, Pagadala Nataraj Sekhar, T. A. Kadam, Marc De Maeyer, A. M. Hashmi, G. Jayasree, Lakkireddy Anandareddy, Tirumalasetty Munichandrababu, P. K. Zubaidha, B. Vijaya Bhaskar, K. Praveen Kumar |
| المصدر: | Medicinal Chemistry Research. 20:930-945 |
| بيانات النشر: | Springer Science and Business Media LLC, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | chemistry.chemical_classification, Aldose reductase, Chemistry, Organic Chemistry, Biological activity, Flavones, chemistry.chemical_compound, Enzyme, Biochemistry, Docking (molecular), Sorbinil, General Pharmacology, Toxicology and Pharmaceutics, Site-directed mutagenesis, Aldehyde Reductase |
| الوصف: | The enzyme aldoreductase which plays an important role in pathogenesis of diabetic retinopathy, neuropathy, and nephropathy was purified from bovine lens, and its inhibitory activity was studied with the synthesized flavone derivatives 1-(2-hydroxyphenyl)ethanone as the starting material. Experimental study revealed that 2-chloroflavone shows less inhibitory activity of 60–70% than other flavones used in the study. To validate experimental results computationally, docking studies of new flavone derivatives synthesized were performed with the enzyme aldose reductase, and the results indicate that 3-iodo, 4-methyl, 5-chloroflavone and 2-chloroflavone bind with higher and lesser affinities. Docking studies with site directed mutagenesis of Val47Ile, Tyr48His, Pro121Phe, Trp219Tyr, Cys298Ala, Leu300Pro, Ser302Arg, and Cys303Asp of the enzyme altered the inhibition activity of aldose reductase. The regression value (R2) of 0.81 between the docking scores of the known inhibitors and the experimental logIC50 indicates the reliability of the docking studies. Biological activity and carcinogenic properties predict that 3-iodo, 4-methyl, 5-chloroflavone is the best flavone inhibitor against aldose reductase. |
| تدمد: | 1554-8120 1054-2523 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::7d5f2190edf4d7fb6a4aad65e788d990Test https://doi.org/10.1007/s00044-010-9412-4Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi...........7d5f2190edf4d7fb6a4aad65e788d990 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15548120 10542523 |
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