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Synergistic Effect of 5-Nitro-2′-deoxyuridine with Ganciclovir Against Human CytomegalovirusIn Vitro

T. Sudhakar Rao, Robert F. Rando, John H. Huffman, Ganapathi R. Revankar

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Abstract

In this paper we describe a practical synthesis of 5-nitro-2′-deoxyuridine (4) and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-nitrouracil (11). These compounds were then evaluated for their ability to inhibit the growth of human cytomegalovirus (HCMV, strain AD169) in MRC-5 cells using a plaque reduction assay. Compound 11 was unable to inhibit the growth of HCMV at the highest concentration tested (100 μg/mL). However, compound 4 (5-NO2-dU) exhibited marginal activity against HCMV in vitro in a dose-dependent manner with a 50% inhibitory concentrations (IC50) of 1 to 5 μg/mL. Combinations of 5-NO2-dU with ganciclovir synergistically inhibited HCMV induced cell killing in culture.

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What this paper is about

In this paper we describe a practical synthesis of 5-nitro-2′-deoxyuridine (4) and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-nitrouracil (11). These compounds were then evaluated for their ability to inhibit the growth of human cytomegalovirus (HCMV, strain AD169) in MRC-5 cells using a plaque reduction assay. Compound 11 was unable to inhibit the growth of HCMV at the highest concentration tested (100 μg/mL). However, compound 4 (5-NO2-dU) exhibited marginal activity against HCMV in vitro in a dose-dependent manner with a 50% inhibitory concentrations (IC50) of 1 to 5 μg/mL. Combinations of 5-NO2-dU with ganciclovir synergistically inhibited HCMV induced cell killing in culture.

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Available abstract

In this paper we describe a practical synthesis of 5-nitro-2′-deoxyuridine (4) and 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-nitrouracil (11). These compounds were then evaluated for their ability to inhibit the growth of human cytomegalovirus (HCMV, strain AD169) in MRC-5 cells using a plaque reduction assay. Compound 11 was unable to inhibit the growth of HCMV at the highest concentration tested (100 μg/mL). However, compound 4 (5-NO2-dU) exhibited marginal activity against HCMV in vitro in a dose-dependent manner with a 50% inhibitory concentrations (IC50) of 1 to 5 μg/mL. Combinations of 5-NO2-dU with ganciclovir synergistically inhibited HCMV induced cell killing in culture.

Key concepts: Ganciclovir, Human cytomegalovirus, In vitro, Deoxyuridine, Chemistry, Nitro, IC50, Cytomegalovirus

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Synergistic Effect of 5-Nitro-2′-deoxyuridine with Ganciclovir Against Human CytomegalovirusIn Vitro — Research Paper | ScholarLens