Title: Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy
Authors: Sekhar, Pagadala Nataraj ×
Kishor, P. B. Kavi
Zubaidha, P. K
Hashmi, A. M
Kadam, T. A
Anandareddy, Lakkireddy
De Maeyer, Marc
Kumar, K. Praveen
Bhaskar, B. Vijaya
Munichandrababu, T
Jayasree, G
Narayana, P. V. B. S
Gyananath, G #
Issue Date: Sep-2011
Publisher: Birkhäuser Boston
Series Title: Medicinal Chemistry Research vol:20 issue:7 pages:930-945
Abstract: 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 (R (2)) of 0.81 between the docking scores of the known inhibitors and the experimental logIC(50) 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.
ISSN: 1054-2523
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry, Molecular and Structural Biology Section
× corresponding author
# (joint) last author

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