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Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling, synthesis and biological testing

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Abstract

The problem of designing new antiviral drugs against Human Cytomegalovirus (HCMV) was addressed using the Online Chemical Modeling Environment (OCHEM). Data on compound antiviral activity to human organisms were collected from the literature and uploaded in the OCHEM database. The predictive ability of the regression models was tested through cross-validation, giving coefficient of determination q2 = 0.71–0.76. The validation of the models using an external test set proved that the models can be used to predict the activity of newly designed compounds with reasonable accuracy within the applicability domain (q2 = 0.70–0.74). The models were applied to screen a virtual chemical library of imidazole derivatives, which was designed to have antiviral activity. The six most promising compounds were identified, synthesized and their antiviral activities against HCMV were evaluated in vitro. However, only two of them showed some activity against the HCMV AD169 strain.

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Data availability

The data used in this work and developed models are freely available online at OCHEM http://ochem.eu/article/135457.

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Acknowledgements

These studies were funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN75N93019D00016 (SHJ). This work was supported by the National Research Foundation of Ukraine (Grant Number 2020.01/0075).

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Authors and Affiliations

  1. V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, 1 Murmanska Str, Kyiv, 02094, Ukraine

    Vasyl Kovalishyn, Volodymyr Zyabrev, Maryna Kachaeva & Volodymyr Brovarets

  2. Institute of Organic Chemistry, National Academy of Sciences, 5, Murmanska Str, Kyiv, 02660, Ukraine

    Kostiantyn Ziabrev

  3. Click Chemistry Tools, East Gelging Dr, Scottsdale, AZ, 834185260, USA

    Kostiantyn Ziabrev

  4. Department of Pediatrics, Division of Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, 35233, USA

    Kathy Keith, Emma Harden, Caroll Hartline & Scott H. James

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  1. Vasyl Kovalishyn
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  2. Volodymyr Zyabrev
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  3. Maryna Kachaeva
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  4. Kostiantyn Ziabrev
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  8. Scott H. James
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  9. Volodymyr Brovarets
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Correspondence to Vasyl Kovalishyn.

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Kovalishyn, V., Zyabrev, V., Kachaeva, M. et al. Design of new imidazole derivatives with anti-HCMV activity: QSAR modeling, synthesis and biological testing. J Comput Aided Mol Des 35, 1177–1187 (2021). https://doi.org/10.1007/s10822-021-00428-z

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  • DOI: https://doi.org/10.1007/s10822-021-00428-z

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