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Development of multiple QSAR models for consensus predictions and unified mechanistic interpretations of the free-radical scavenging activities of chromone derivatives

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Abstract

Antioxidants are important defenders of the human body against nocive free radicals, which are the causative agents of most life-threatening diseases. The immense biomedicinal utility of antioxidants necessitates the development and design of new synthetic antioxidant molecules. The present report deals with the modeling of a series of chromone derivatives, which was done to provide detailed insight into the main structural fragments that impart antioxidant activity to these molecules. Four different quantitative structure–property relationship (QSAR) techniques, namely 3D pharmacophore mapping, comparative molecular similarity indices analysis (CoMSIA 3D-QSAR), hologram QSAR (HQSAR), and group-based QSAR (G-QSAR) techniques, were employed to obtain statistically significant models with encouraging external predictive potentials. Moreover, the visual contribution maps obtained for the different models signify the importance of different structural features in specific regions of the chromone nucleus. Additionally, the G-QSAR models determine the composite influence of pairs of substituent fragments on the overall antioxidant activity profiles of the molecules. Multiple models with different strategies for assessing structure–activity relationships were applied to reach a unified conclusion regarding the antioxidant mechanism and to provide consensus predictions, which are more reliable than values derived from a single model. The structural information obtained from the various QSAR models developed in the present work can thus be effectively utilized to design and predict the activities of new molecules belonging to the class of chromone derivatives.

Schematic diagram showing different features at various positions favoring the antioxidant activity profiles of the chromone derivatives, as well as the different QSAR techniques adopted to reach the conclusions

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Acknowledgments

This research work is supported in the form of a major research project to K.R. and a senior research fellowship to I.M. by the Indian Council of Medical Research (ICMR), New Delhi. We thank the anonymous reviewers for useful comments. The authors thank VLife Sciences Technologies Pvt. Ltd., Pune for providing complimentary evaluation license of the software VLife MDS 3.5.

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Authors and Affiliations

  1. Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700 032, India

    Indrani Mitra & Kunal Roy

  2. Department of Chemical Technology, University College of Science and Technology, University of Calcutta, 92, A.P.C. Road, Kolkata, 700 009, India

    Achintya Saha

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  1. Indrani Mitra
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Correspondence to Kunal Roy.

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Mitra, I., Saha, A. & Roy, K. Development of multiple QSAR models for consensus predictions and unified mechanistic interpretations of the free-radical scavenging activities of chromone derivatives. J Mol Model 18, 1819–1840 (2012). https://doi.org/10.1007/s00894-011-1198-x

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