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In vitro activity of novel derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile against human cytomegalovirus

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Abstract

Ten 5-functionalized derivatives of 1,3-oxazole-4-carboxylate and 1,3-oxazole-4-carbonitrile were synthesized and their antiviral activities against the human cytomegalovirus (HCMV) were evaluated in vitro. Bioassays showed that seven compounds exhibited considerably higher antiviral activity (EC50: < 0.05 μM) against a normal laboratory HCMV strain (AD-169) in human foreskin fibroblast cells than Ganciclovir (EC50 = 0.32 μM), an anti-HCMV agent in clinical use. Additionally, the HCMV-resistant isolate (GDGr K17) was tested for sensitivity to 1,3-oxazole derivatives with most antiviral potency against the strain AD169. A one of them (5-((2-hydroxyethyl)(methyl)amino)-2-(4-methylphenyl)-1,3-oxazole-4-carbonitrile) showed very high potency (EC50: < 0.05; CC50: >150 µM, and SI50 = 3125) towards the resistant isolate compared to standard drugs Cidofovir (EC50 = 0.10 µM, CC50: >30 µM and SI50: <4). But, in contrast to the primary assays, the antiviral activity of these compounds against both the normal strain and the resistant isolate of HCMV were considerably less than one of Cidofovir in secondary assay. These results provided evidence that derivatives of 1,3-oxazole could be useful for developing new anti-HCMV drugs.

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Acknowledgements

We would like to thank Enamine Ltd. for the material and technical support. These studies were funded in whole or in part with Federal funds from the National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract HHSN272201100016I (MNP).

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Authors and Affiliations

  1. Department of Chemistry of Bioactive Nitrogen-Containing Heterocyclic Bases, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, 1, Murmanskaya str, Kyiv, 02094, Ukraine

    Maryna V. Kachaeva, Stepan G. Pilyo, Victor V. Zhirnov & Volodymyr S. Brovarets

  2. Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA

    Caroll B. Hartline, Emma A. Harden & Mark N. Prichard

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  1. Maryna V. Kachaeva
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  2. Stepan G. Pilyo
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  3. Caroll B. Hartline
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  4. Emma A. Harden
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  5. Mark N. Prichard
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  6. Victor V. Zhirnov
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  7. Volodymyr S. Brovarets
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Correspondence to Volodymyr S. Brovarets.

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Kachaeva, M.V., Pilyo, S.G., Hartline, C.B. et al. 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 (2019). https://doi.org/10.1007/s00044-019-02365-x

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