Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Dec;35(12):1177-1187.
doi: 10.1007/s10822-021-00428-z. Epub 2021 Nov 12.

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

Vasyl Kovalishyn  1 , Volodymyr Zyabrev  2 , Maryna Kachaeva  2 , Kostiantyn Ziabrev  3   4 , Kathy Keith  5 , Emma Harden  5 , Caroll Hartline  5 , Scott H James  5 , Volodymyr Brovarets  2
Affiliations

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

Vasyl Kovalishyn et al. J Comput Aided Mol Des. 2021 Dec.

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.

Keywords: Antiviral activity; Human cytomegalovirus (HCMV); Imidazole derivatives; Machine learning; OCHEM.

PubMed Disclaimer

References

    1. Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H (2009) Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep 58:1–207 - PubMed
    1. Griffiths P, Baraniak I, Reeves M (2015) The pathogenesis of human cytomegalovirus. J Pathol 235:288–297 - DOI
    1. Gugliesi F, Pasquero S, Griffante G, Scutera S, Albano C, Pacheco SFC, Riva G, Dell’Oste V, Biolatti M (2021) Human cytomegalovirus and autoimmune diseases: Where are we? Viruses 13(2):260 - DOI
    1. Kovalishyn V, Grouleff J, Semenyuta I, Sinenko VO, Slivchuk SR, Hodyna D, Brovarets V, Blagodatny V, Poda G, Tetko IV, Metelytsia L (2018) Rational design of isonicotinic acid hydrazide derivatives with antitubercular activity: Machine learning, molecular docking, synthesis and biological testing. Chem Biol Drug Des. https://doi.org/10.1111/cbdd.13188 - DOI - PubMed
    1. Kachaeva MV, Pilyo SG, Hartline CB, Harden EA, Prichard MN, Zhirnov VV, Brovarets VS (2019) In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus. Med Chem Res 28:1205–1211 - DOI

Publication types

LinkOut - more resources