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Research and study of 2-((4,6 dimethyl pyrimidine-2-yle) thio)-N-phenyl acetamide derivatives as inhibitors of sirtuin 2 protein for the treatment of cancer using QSAR, molecular docking and molecular dynamic simulation

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Abstract 

Phenyl acetamide derivatives have a wide range of biological activities, so their research and development can be useful and effective for the design production of new drugs. In this project, quantitative structure–activity relationship (QSAR) was performed. For modeling two methods of multiple linear regression (MLR) and nonlinear regression of support vector machine (SVR) were used. In the MLR stage, the best model with the values of R2train = 0.913 and R2test = 0.881 was selected by stepwise method. In this model, 4 descriptors of BELV2, GATS8p, GATS6e and RDF080m were included, which were used as input for the nonlinear support vector regression method. In the SVR model, the best results were obtained using the radial Gaussian kernel function (RBF) with R2train = 0.978 and R2test = 0.990. In the next step, using molecular docking and molecular dynamic simulation methods, the interaction between phenyl acetamide derivatives and the sirtuin 2 protein was investigated. Examining the results of molecular docking, it was observed that these derivatives formed complexes by forming hydrogen and hydrophobic bonds with the sirtuin 2 protein. Also, the results of molecular dynamic simulation show that phenyl acetamide compounds form stable complex with the sirtuin 2 protein, and it was found that the compounds with more activity have formed a number of hydrogen bonds with the protein.

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Acknowledgements

The authors gratefully acknowledge the Shahid Bahonar University of Kerman.

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Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran

    Sahar Ilaghi-Hoseini & Zahra Garkani-Nejad

  2. Young Researchers Society, Shahid Bahonar University of Kerman, Kerman, Iran

    Sahar Ilaghi-Hoseini

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  1. Sahar Ilaghi-Hoseini
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  2. Zahra Garkani-Nejad
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Contributions

S. I. contributed to QSAR analysis, molecular docking and molecular dynamic simulation analysis, and writing the first draft of the manuscript. Z. G. contributed to project administration, supervision, methodology, interpretation of the results, reviewing, and editing.

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Correspondence to Zahra Garkani-Nejad.

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Ilaghi-Hoseini, S., Garkani-Nejad, Z. Research and study of 2-((4,6 dimethyl pyrimidine-2-yle) thio)-N-phenyl acetamide derivatives as inhibitors of sirtuin 2 protein for the treatment of cancer using QSAR, molecular docking and molecular dynamic simulation. J Mol Model 28, 343 (2022). https://doi.org/10.1007/s00894-022-05288-4

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