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DFT-based QSAR and QSPR models of several cis-platinum complexes: solvent effect

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Abstract

Cytotoxic activities of cis-platinum complexes against parental and resistant ovarian cancer cell lines were investigated by quantitative structure-activity relationship (QSAR) analysis using density functional theory (DFT) based descriptors. The calculated parameters were found to increase the predictability of each QSAR model with incorporation of solvent effects indicating its importance in studying biological activity. Given the importance of logarithmic n-octanol/water partition coefficient (log P o/w) in drug metabolism and cellular uptake, we modeled the log P o/w of 24 platinum complexes with different leaving and carrier ligands by the quantitative structure-property relationship (QSPR) analysis against five different concentrations of MeOH using DFT and molecular mechanics derived descriptors. The log P o/w values of an additional set of 20 platinum complexes were also modeled with the same descriptors. We investigated the predictability of the model by calculating log P o/w of four compounds in the test set and found their predicted values to be in good agreement with the experimental values. The QSPR analyses performed on 24 complexes, combining the training and test sets, also provided significant values for the statistical parameters. The solvent medium played an important role in QSPR analysis by increasing the internal predictive ability of the models.

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Acknowledgments

The authors thank Council of Scientific and Industrial Research (CSIR), New Delhi and Department of Science and Technology (DST), New Delhi for some financial support. The authors also thank Mrs Surobhi Deka, Department of Mathematical Sciences, Tezpur University for fruitful discussion.

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Authors and Affiliations

  1. Department of Chemical Sciences, Tezpur University, Napaam, Tezpur, Assam, 784028, India

    Pubalee Sarmah & Ramesh C. Deka

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  1. Pubalee Sarmah
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  2. Ramesh C. Deka
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Correspondence to Ramesh C. Deka.

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Sarmah, P., Deka, R.C. DFT-based QSAR and QSPR models of several cis-platinum complexes: solvent effect. J Comput Aided Mol Des 23, 343–354 (2009). https://doi.org/10.1007/s10822-009-9265-4

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  • DOI: https://doi.org/10.1007/s10822-009-9265-4

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