Pinizzotto M R, Garozzo A, Guerrera F, Castro A, La Rosa M G, Furneri P M, Geremia E
Institute of Microbiology, University of Catania, Italy.
Antiviral Res. 1992 Jul 1;19(1):29-41. doi: 10.1016/0166-3542(92)90054-9.
The in vitro effects of four isothiazoles [5,5'-diphenyl-3,3'-diisothiazole disulfide, 5-phenyl-3-mercapto-isothiazole, 5,5'-(4-chlorophenyl)-3,3'- diisothiazole disulfide, and 5-(4-chlorophenyl)-3-mercapto-isothiazole] on poliovirus type 1 were studied. The derivatives tested demonstrated remarkable viral inhibition, with a higher selectivity index than the previously studied iminodithiole precursors. Under one-step growth conditions, all the isothiazole derivatives caused the greatest activity if added during or after (within 1 h) poliovirus adsorption. These data suggest interference with early events of viral replication. [5-3H]Uridine incorporation into RNA showed that the compounds tested reduced poliovirus RNA synthesis, which was completely shut off after 2 h of incubation and reduced by 50-60% after 4 h. Also, pretreatment of the cell cultures with the compounds for 24 h caused a substantial inhibition of viral replication. The data suggest that the four isothiazole derivatives may have a multi-step antiviral mode of action different from their iminodithiole precursors.
研究了四种异噻唑类化合物[5,5'-二苯基-3,3'-二异噻唑二硫化物、5-苯基-3-巯基异噻唑、5,5'-(4-氯苯基)-3,3'-二异噻唑二硫化物和5-(4-氯苯基)-3-巯基异噻唑]对1型脊髓灰质炎病毒的体外作用。所测试的衍生物表现出显著的病毒抑制作用，其选择性指数高于先前研究的亚氨基二硫醇前体。在一步生长条件下，如果在脊髓灰质炎病毒吸附期间或之后（1小时内）添加所有异噻唑衍生物，则会产生最大活性。这些数据表明其对病毒复制早期事件存在干扰。[5-³H]尿苷掺入RNA显示，所测试的化合物可减少脊髓灰质炎病毒RNA合成，孵育2小时后RNA合成完全停止，4小时后减少50-60%。此外，用这些化合物对细胞培养物进行24小时预处理可显著抑制病毒复制。数据表明，这四种异噻唑衍生物可能具有与亚氨基二硫醇前体不同的多步骤抗病毒作用模式。
