ANTIADENOVIRALACTIVITY OF FLUORIDECONTAINING NUCLEOSIDES AND BISPHOSPHONATES DERIVATES

Abstract

Human adenoviruses cause various acute diseases including gastrointestinal and respiratory disorders. However, there are no clinically approved specific antiadenoviral drugs. Therefore, the search of drugs and regimens that would be effective, safe for prolonged use, and available at a cost to a wide range of patients is extremely important. The aim of the work was to study the cytotoxicity and antiviral activity of six new fluorochemical compounds with respect to human adenovirus serotype 5 in vitro. Methods. Cytotoxicity of the compounds was determined by MTT-test. The lysosomal activity of cells was estimated using neutral red dye. Cytomorphological method was used to identify adenovirus infected cells containing specific virus inclusion. In addition, the anti-adenoviral activity of the most effective compounds was confirmed by real-time PCR analysis. Results. CC50 index measured by MTT- test, ranged from 125 mg/ml to 1000 μg/ml. CC50 index determined with neutral red dye ranged from 630 μg/ml to 2500 μg/ml. It was discovered that the toxicity of compounds dependent on their solubility. The anti-adenoviral activity was shown for three compounds referred to G22, G26 and 10S-23 with EC 50 values of 60, 120 and 90 μg/ml, respectively. PCR analysis also revealed anti-adenoviral activity of the compounds G26 and 10S-23. Conclusions. The analysis of the cytotoxic and antiviral activity of six new fluorochemical compounds was conducted. Cytomorphological analysis showed the antiviral activity against adenovirus serotype 5 for the compounds G22, G26 and 10S-23. Using PCR analysis, the anti-adenoviral activity of the compounds G26 and 10S-23 was demonstrated.

Keywords

• аденовірус
• фторвмісні сполуки
• цитотоксичність
• антивірусна активність