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Biological activity of some ACAT inhibitors in the light of DFT-based quantum descriptors

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Abstract

A detailed investigation is performed for a series of 24 aminosulfonyl carbamates as acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors. The biological activity of aminosulfonyl carbamates in terms of log (IC50) has been estimated by developing suitable quantum chemical descriptors in the light of density functional theory. In order to understand inhibitor-biosystem interactions and to identify potential descriptors, a model biosystem is considered which comprises five different nucleic acid bases. Accordingly, two global descriptors, viz. electron affinity (EA) and energy transfer during the interaction between inhibitors and biosystems (∆E), and a local descriptor, viz. group atomic charges on sulfonyl moiety (∑QSul), are developed toward understanding bio-activity of aminosulfonyl carbamates. It is noteworthy to achieve that the three-parameter regression model for considered parameters EA, ∆E, and ∑QSul is observed to predict about 90% activities of aminosulfonyl carbamates in terms of log(IC50). The developed regression model is also statistically validated and successfully tested for unknown compounds.

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Funding

BKS received UGC-RGNF fellowship (RGNF-2017-18-SC-GUJ-35487). DRR received financial support from the SERB, New Delhi, Govt. of India (Grant No. EMR/2016/005830).

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Authors and Affiliations

  1. Department of Chemistry, Uka Tarsadia University, Tarsadi, 394 350, India

    Sutapa Mondal Roy

  2. Department of Applied Physics, S. V. National Institute of Technology, Materials and Biophysics Group, Surat, 395007, India

    Bhumika K. Sharma & Debesh R. Roy

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  1. Sutapa Mondal Roy
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  2. Bhumika K. Sharma
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  3. Debesh R. Roy
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Correspondence to Sutapa Mondal Roy or Debesh R. Roy.

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Roy, S.M., Sharma, B.K. & Roy, D.R. Biological activity of some ACAT inhibitors in the light of DFT-based quantum descriptors. Struct Chem 30, 2379–2387 (2019). https://doi.org/10.1007/s11224-019-01348-3

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