Novel Cationic Meso-Arylporphyrins and Their Antiviral Activity Against HSV-1

Pharmaceuticals

AllaA. Babayants¹  OlgaN. Scheglovitova¹  IrinaS. Frolova¹  NadezhdaI. Filippova¹  NadezhdaN. Scliankina¹  AndreyP. Zhdanov²  IngaO. Savelyeva³  KseniyaA. Zhdanova³  ArtemV. Ezhov³  Natal’yaA. Bragina³  AndreyF. Mironov³  KonstantinYu. Zhizhin³ 

[1] Gamaleya Research Center of Epidemiology and Microbiology, Gamaleya Str. 18, Moscow 123098, Russia;Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, Leninskii Pr. 31, Moscow 117907, Russia;MIREA—Russian Technological University, Vernadsky Prospect 86, Moscow 119571, Russia;

关键词: viruses;    antiviral activity;    synthesis;    cationic porphyrins;    anti-HSV-1;    dark antiviral activity of porphyrins;   

DOI  :  10.3390/ph14030242

来源: DOAJ

【 摘 要 】

This work is devoted to the search for new antiherpes simplex virus type 1 (HSV-1) drugs among synthetic tetrapyrroles and to an investigation of their antiviral properties under nonphotodynamic conditions. In this study, novel amphiphilic 5,10,15,20-tetrakis(4-(3-pyridyl-n-propanoyl)oxyphenyl)porphyrin tetrabromide (3a), 5,10,15,20-tetrakis(4-(6-pyridyl-n-hexanoyl)oxyphenyl)porphyrin tetrabromide (3b) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (TMePyP) were synthesized, and their dark antiviral activity in vitro against HSV-1 was studied. The influence of porphyrin’s nanosized delivery vehicles based on Pluronic F127 on anti-HSV-1 activity was estimated. All the received compounds 3a, 3b and TMePyP showed virucidal efficiency and had an effect on viral replication stages. The new compound 3b showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum TMePyP activity was observed with a high concentration; porphyrin 3a was the least active. The inclusion of the synthesized compounds in Pluronic F-127 polymeric micelles had a noticeable effect on antiviral activity only at higher porphyrin concentrations. Action of the received compounds differs by influence on the early or later reproduction stages. While 3a and TMePyP acted on all stages of the viral replication cycle, porphyrin 3b inhibited viral replication during the early stages of infection. The resulting compounds are promising for the development of utilitarian antiviral agents and, possibly, medical antiviral drugs.

【 授权许可】

Unknown