کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2511036 | 1118002 | 2008 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections?: Lack of efficacy of promazine on SARS-CoV replication in a mouse model Is the anti-psychotic, 10-(3-(dimethylamino)propyl)phenothiazine (promazine), a potential drug with which to treat SARS infections?: Lack of efficacy of promazine on SARS-CoV replication in a mouse model](/preview/png/2511036.png)
Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC90 = 8.3 ± 2.8 μM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC90 = 6.1 ± 4.3 μM). All compounds were toxic (IC50 = 6.6–74.5 μM) except for phenoxathiin (IC50 = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine·HCl (IC50 = 195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1–3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (−4 h)/therapeutic regimen of 1, 10, or 50 mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reducing virus replication. Therefore, treating SARS infections with compounds like promazine is not warranted.
Journal: Antiviral Research - Volume 79, Issue 2, August 2008, Pages 105–113