用于红细胞病毒灭活的酚噻嗪类光敏剂的筛选

Screening of phenothiazine photosensitizers that can be used to inactivate viruses in red blood cells

目的 筛选用于红细胞病毒灭活的光敏剂 ,并研究酚噻嗪类光敏剂的构效关系。方法 以Phi6噬菌体为模型病毒 ,以红细胞溶血及钾泄漏作为红细胞损伤指标 ,研究一系列新合成的酚噻嗪类化合物以及亚甲蓝(MB)、二甲基亚甲蓝 (DMMB)的病毒灭活能力和对红细胞的损伤情况。结果 灭活Phi6噬菌体的能力DMMB >M0 0 7>M0 0 9>MB >M0 1 6 >M0 1 2 >M0 1 3 >M0 1 1 >M0 0 4 >M0 0 2 >M0 0 3 >M0 1 5 =M0 0 1 ;在灭活 6Log1 0Phi6噬菌体的条件下 ,对红细胞的损伤DMMB <M0 0 7<M 0 0 9<MB。使用灭活 6Log1 0Phi6噬菌体的光照剂量 ,DMMB可以灭活 >6 .5Log1 0水疱性口炎病毒 (VSV)、>7.0Log1 0I型单纯疱疹病毒 (HSV Ⅰ )、>9.9Log1 0R 1 7噬菌体 ;M0 0 7可以灭活 >6 .5Log1 0VSV、>5 .0Log1 0HSV Ⅰ、>9.9Log1 0R 1 7噬菌体。 结论 酚噻嗪环上烷基化修饰可以提高光敏剂的病毒灭活能力 ,减少对红细胞的损伤。M0 0 7可能是继DMMB之后又一个具有潜在应用前景的酚噻嗪类光敏剂。

To research the effect of structure modification of phenothiazine dyes,and to find a photosensitizer that can be used for virus inactivation in red blood cells.Methods Using bacteriophage Phi6 as a model virus,measuring potassium efflux and hemolysis as the parameters of damage to red blood cells,a series of new synthesized phenothiazine derivatives and methylene blue(MB),dimethylmethylene blue(DMMB)were tested for their abilities of virus inactivation and damage to red blood cells.Results The ability of inactivating bacteriophage Phi6 was as follow:DMMB>M007>M009>MB>M016>M012>M013>M011>M004>M002>M003>M015=M001;at the condition of inactivating 6Log10 Phi6,red blood cell damage caused by these photosensitizers was DMMB<M007<M009<MB.When illuminated with the light dose of inactivating 6Log10 Phi6,DMMB can inactivate >6.5Log10 vesicular stomatitis virus (VSV)?>7.0Log10 herpes simplex virus(HSV Ⅰ)?>9.9Log10 bacteriophage R 17; M007 can inactivate >6.5Log10 vesicular stomatitis virus (VSV)?>5.0 Log10 herpes simplex virus(HSV Ⅰ)?>9.9Log10 bacteriophage R 17 Conclusion Alkylation of the phenothiazine ring increased the potential of inactivating virus and decreased the damage to red blood cells? M007 might be an alternative phenothiazine dye that can be used to inactivate viruses in red blood cells?