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

• Main Authors: Kseniya A. Zhdanova (Author), Inga O. Savelyeva (Author), Artem V. Ezhov (Author), Andrey P. Zhdanov (Author), Konstantin Yu. Zhizhin (Author), Andrey F. Mironov (Author), Natal'ya A. Bragina (Author), Alla A. Babayants (Author), Irina S. Frolova (Author), Nadezhda I. Filippova (Author), Nadezhda N. Scliankina (Author), Olga N. Scheglovitova (Author)
• Format: Book
• Published: MDPI AG, 2021-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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-<i>n</i>-propanoyl)oxyphenyl)porphyrin tetrabromide (<b>3a</b>), 5,10,15,20-tetrakis(4-(6-pyridyl-<i>n</i>-hexanoyl)oxyphenyl)porphyrin tetrabromide (<b>3b</b>) and known 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetraiodide (<b>TMePyP</b>) 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 <b>3a</b>, <b>3b</b> and <b>TMePyP</b> showed virucidal efficiency and had an effect on viral replication stages. The new compound <b>3b</b> showed the highest antiviral activity, close to 100%, with the lowest concentration, while the maximum <b>TMePyP</b> activity was observed with a high concentration; porphyrin <b>3a</b> 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 <b>3a</b> and <b>TMePyP</b> acted on all stages of the viral replication cycle, porphyrin <b>3b</b> 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.

Item Description

10.3390/ph14030242
1424-8247