Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation

Bhawna Vyas; Manjinder Singh; Maninder Kaur; Malkeet Singh Bahia; Amteshwar Singh Jaggi; Om Silakari; Baldev Singh

doi:10.1016/j.jmgm.2015.03.005

Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation

Bhawna Vyas, Manjinder Singh, Maninder Kaur, Malkeet Singh Bahia, Amteshwar Singh Jaggi, Om Silakari, Baldev Singh

Punjabi University

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

Herein, atom-based 3D-QSAR analysis was performed using receptor-guided alignment of 46 flavonoid inhibitors of aldose reductase (ALR2) enzyme. 3D-QSAR models were generated in PHASE programme, and the best model corresponding to PLS factor four (QSAR₄), was selected based on different statistical parameters (i.e., Rtrain2, 0.96; Qtest2 0.81; SD, 0.26). The contour plots of different structural properties generated from the selected model were utilized for the designing of five new congener molecules. These designed molecules were duly synthesized, and evaluated for their in vitro ALR2 inhibitory activity that resulted in the micromolar (IC₅₀ < 22 μM) activity of all molecules. Thus, the newly designed molecules having ALR inhibitory potential could be employed for the management of diabetic complications.

Original language	English
Pages (from-to)	59-71
Number of pages	13
Journal	Journal of Molecular Graphics and Modelling
Volume	59
DOIs	https://doi.org/10.1016/j.jmgm.2015.03.005
State	Published - 1 Jun 2015
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Inc. All rights reserved.

Funding

The authors thank Dr. Ravikumar Muttineni (Application Scientist), Er. Anirban Banerjee (IT Consultant), and Mr. Raghu Rangaswamy from Schrödinger, Bangalore, for their constant scientific and technical support to handle Schrödinger software and work smoothly. Bhawna Vyas and Malkeet Singh acknowledges Indian Council of Medical Research (ICMR) , New Delhi, for providing Senior Research Fellowship (SRF); Grant No. 45/15/2011/BIF/BMS and 45/3/2012-BMS/BIF , respectively.

Funders	Funder number
Indian Council of Medical Research	45/3/2012-BMS/BIF, 45/15/2011/BIF/BMS

Keywords

Aldose reductase (ALR2)
Atom-based 3D-QSAR
Diabetic complications
Docking analysis
Flavonoid derivatives

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.jmgm.2015.03.005

Cite this

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title = "Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation",

abstract = "Herein, atom-based 3D-QSAR analysis was performed using receptor-guided alignment of 46 flavonoid inhibitors of aldose reductase (ALR2) enzyme. 3D-QSAR models were generated in PHASE programme, and the best model corresponding to PLS factor four (QSAR4), was selected based on different statistical parameters (i.e., Rtrain2, 0.96; Qtest2 0.81; SD, 0.26). The contour plots of different structural properties generated from the selected model were utilized for the designing of five new congener molecules. These designed molecules were duly synthesized, and evaluated for their in vitro ALR2 inhibitory activity that resulted in the micromolar (IC50 < 22 μM) activity of all molecules. Thus, the newly designed molecules having ALR inhibitory potential could be employed for the management of diabetic complications.",

keywords = "Aldose reductase (ALR2), Atom-based 3D-QSAR, Diabetic complications, Docking analysis, Flavonoid derivatives",

author = "Bhawna Vyas and Manjinder Singh and Maninder Kaur and Bahia, {Malkeet Singh} and Jaggi, {Amteshwar Singh} and Om Silakari and Baldev Singh",

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AU - Vyas, Bhawna

AU - Singh, Manjinder

AU - Kaur, Maninder

AU - Bahia, Malkeet Singh

AU - Jaggi, Amteshwar Singh

AU - Silakari, Om

AU - Singh, Baldev

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KW - Diabetic complications

KW - Docking analysis

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Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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