Relationship Between Conformation and Antiviral Activity-III. 3′-Azidothymidine (AZT) and 3′-Azido-2′, 3′-dideoxy-5-hydroxymethyluridine |
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| Authors: | Sagar V Gupta Sashi VP Kumar Allan L Stuart Ruili Shi Keith C Brown Wajdi M Zoghaib |
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| Institution: | 1. Department of Veterinary Physiological Sciences , University of Saskatchewan , Saskatoon, Saskatchewan, Canada , S7N 5B4;2. Department of Chemistry , University of Saskatchewan , Saskatoon, Saskatchewan, Canada , S7N 5B4 |
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| Abstract: | Abstract 3′-Azido-2′,3′-dideoxy-5-hydroxymethyluridine (AZHMddUrd) was synthesized to improve the potency of 5-hydroxymethyl-2′-deoxyuridine (HMdUrd) against human immunodeficiency virus (HIV). AZHMddUrd was a very poor inhibitor of HIV replication (ED50 >200 μM) and was also nontoxic up to 400 μM (highest concentration tested) to HT4-6C (HeLa CD4) cells. AZT was phosphorylated by human cellular thymidine kinase. In contrast, AZHMddUrd and HMdUrd were poor substrates for the kinase. The relationship between molecular conformation and antiretroviral activity for 3′-azidothymidine (AZT), HMdUrd and AZHMddUrd is discussed. |
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