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Insights into activity enhancement of 4-aminoquinoline-based hybrids using atom-based and field-based QSAR studies

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Abstract

Malaria has remained one of the most devastating diseases, and the problem has further complicated due to wide spread of chloroquine (CQ)-resistance strain of Plasmodium falciparum. In order to overcome this problem, efforts are being made to develop new chemical entities that can solve the problem of drug resistance. In this context, both atom-based and field-based 3D-QSAR (3-Dimensional quantitative structure–activity relationship) studies were carried out for some of our recently reported 4-aminoquinoline hybrids. The four models generated have shown good correlation coefficients r 2 (0.97, 0.97, 0.94, and 0.95) and test set prediction coefficients q 2 (0.86, 0.88, 0.93, and 0.89). The 3D-QSAR models gave insights into the facts about the changes in the activity pattern with the change in pyrimidine, triazine, and triazole rings. These models will be useful in the future projects of developing new antimalarial compounds against both the CQ-sensitive and CQ-resistance strains of P. falciparum.

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Acknowledgments

DSR thanks University Grants Commission [F. No. 41-202/2012(SR)], New Delhi, India and University of Delhi, Delhi, India for financial support. KKR and SM are thankful to CSIR for the award of research associate ship and senior research fellowship, respectively. Authors thank Dr. M Ravi Kumar (Senior Application Scientist, Schrodinger. Inc, USA) for his suggestions.

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Authors and Affiliations

  1. Department of Chemistry, University of Delhi, Delhi, 110007, India

    K. Kranthi Raj, Sunny Manohar & Diwan S. Rawat

  2. Centre for Bioinformatics, Department of Biotechnology, K L University, Green Fields, Vaddeswaram, India

    Venkateswara Rao Talluri

Authors
  1. K. Kranthi Raj
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  2. Sunny Manohar
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  3. Venkateswara Rao Talluri
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  4. Diwan S. Rawat
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Corresponding author

Correspondence to Diwan S. Rawat.

Supplementary Data

44_2014_1195_MOESM1_ESM.doc

Electronic Supplementary Information (ESI) available: [Field fractions of atom-based and field-based 3D-QSAR models and other information mentioned in manuscript]. Supplementary material 1 (DOC 267 kb)

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Kranthi Raj, K., Manohar, S., Talluri, V.R. et al. Insights into activity enhancement of 4-aminoquinoline-based hybrids using atom-based and field-based QSAR studies. Med Chem Res 24, 1136–1154 (2015). https://doi.org/10.1007/s00044-014-1195-6

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  • DOI: https://doi.org/10.1007/s00044-014-1195-6

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