Comparative activity of various compounds against clinical strains of herpes simplex virus
Tóm tắt
The following compounds were evaluated for their inhibitory activity against clinical strains of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in both primary rabbit kidney (PRK) and HeLa cell cultures: (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA), 9-(2-phosphonylmethoxyethyl)adenine (PMEA), (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), (RS)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine (HPMPDAP), 5-(5-bromothien-2-yl)-2′-deoxyuridine (BTDU), 5-(5-chlorothien-2-yl)-2′-deoxyuridine (CTDU), 9-(2-deoxy-2-hydroxymethyl-β-D-erythro-oxetanosyl)guanine (OXT-G), pentosan polysulfate, heparin, dextran sulfate (MW 10,000), acyclovir, 9-(2-hydroxyethoxymethyl)guanine (ACV), (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU), 1-β-D-arabinofuranosyl-(E)-5-(2-bromovinyl)-uracil (BVaraU), vidarabine (9-β-D-arabinofuranosyladenine) (ara-A) and phosphonoformate (PFA). The most potent inhibitors of HSV-1 were (in order of decreasing activity in PRK cells) BVDU, ACV, BVaraU and OXT-G, their mean 50 % inhibitory concentration (IC50) ranging from 0.02 µg/ml to 0.9 µg/ml. Then followed BTDU and CTDU (IC50 1–2 µg/ml), the sulfated polysaccharides (IC50 1.3–5.8 µg/ml), the phosphonylmethoxyalkyl derivatives (IC50 5.6–25 µg/ml), ara-A (IC50 11 µg/ml) and PFA (IC50 38.5 µg/ml). Except for BVDU, BVaraU, BTDU and CTDU, the compounds did not discriminate between HSV-2 and HSV-1. All the compounds studied could be considered specific anti-HSV agents. Their selectivity indexes varied from 3 (PFA) to 6400 (BVDU).
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