EFFECT OF PHOSPHONIC ACID ANALOGS OF ACYCLOVIR AND GANCICLOVIR ON IN VITRO CYTOMEGALOVIRUS INFECTIONS |
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| Authors: | Robert W Sidwell John H Huffman Dale L Barnard Elmer J Reist |
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| Institution: | 1. Dept. of Animal, Dairy and Veterinary Sciences , Utah State University , Logan, UT, 84322-5600;2. SRI International , Menlo Park, CA, 94025 |
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| Abstract: | Abstract Eight phosphonic acid analogs of acyclovir (ACV) or ganciclovir (DHPG) inhibited human cytomegalovirus in vitro. Therapeutic indices were: phosphonate diacid of DHPG: 500; DHPG: 500; phosphonate monoethylester of DHPG: 258; phosphonate monoethylester of ACV: 94; cyclic phosphonate of DHPG: 64; ACV: 60; phosphonate monobutylester of ACV: 1.5; phosphonate monoethylester of deoxy DHPG: 4.6; 8-bromo ACV phosphonate monoethylester: >2; phosphonate monoethylester heptyl of ACV: 1. Types 1 and 2 herpesvirus (HSV-1, HSV-2) and varicella zoster virus (VZV) were poorly inhibited by these new compounds, suggesting highly specific anti-HCMV activity. None exhibited significant cytotoxic effects as measured by uptake of 3H]thymidine, 3H]uridine and 3H]leucine. |
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