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

Abstract

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.

Photodynamic Inhibition of Herpes Simplex Virus 1 Infection by Tricationic Amphiphilic Porphyrin with a Long Alkyl Chain

“…Although we found that the compound induces massive cell death when activated by light at concentrations >1 μM, low systemic toxicity was observed in the nanomolar range, which is comparable to other similar compounds [ 45 , 46 , 47 ]. This allowed us to design antiviral assays at subtoxic concentrations, which is highly important to avoid toxicity concerns and to extend the potential application to the inactivation of different viruses in sensitive biological materials (e.g., serum or blood).…”

Cationic Porphyrins as Antimicrobial and Antiviral Agents in Photodynamic Therapy

“…Trans-A2B2 type dicationic porphyrins 31a,b in the form of free base and zinc complex [136] were used to study the effect of the PS structure on photodynamic antibacterial activity. In the study of the photoinduced antibacterial activity of these porphyrins against Staphylococcus aureus strain 78 zinc complex 31b was found to exhibit photodynamic action within the whole concentration range studied, even at a minimum irradiation dose of 2.3 J/cm 2 compared to the free-base porphyrin, which showed lower effi- The antiviral activity of compounds 29a,b against the herpes simplex virus 1 (HSV-1) was also evaluated in our work [137]. Compounds 29a,b and their Pluronic F-127 micellar forms showed virucidal efficiency and affected the different replication stages of HSV-1.…”

“…In our studies [134][135][136][137], we investigated the antimicrobial activity against S. aureus and E. coli bacteria and their biofilms for cationic meso-arylporphyrins with A4 and AB-AB structure with terminal pyridinium groups (Figure 15). In these works, we modified the following parameters in the structure of the compounds: (1) the hydrophilichydrophobic balance varied depending on the number of methylene spacers (2, 4, 5, 10); In our studies [134][135][136][137], we investigated the antimicrobial activity against S. aureus and E. coli bacteria and their biofilms for cationic meso-arylporphyrins with A4 and ABAB structure with terminal pyridinium groups (Figure 15). In these works, we modified the following parameters in the structure of the compounds: We have shown that the efficiency of the used РS decreases with the increasing length of the methylene spacers, which is associated with an increase in their hydrophobicity, and hence with the aggregation processes in aqueous media.…”

Porphyrin-derived carbon dots for an enhanced antiviral activity targeting the CTD of SARS-CoV-2 nucleocapsid

“…Furthermore, this study evaluated the cytotoxicity and antiviral activity of porphyrin and por-CDs against SARS-CoV-2 in mammalian cells. On Vero E6 cells, the CC 50 of porphyrin used in this study (15.5 μg/mL, equivalent to 49.94 μM where the molecular weight of porphyrin is 310.352 g/mol) was much higher than the other porphyrin derivatives: verteporfin (10.33 μM) [ 43 ], Sn-protoporphyrin IX (20.7 μM) [ 55 ], and a novel meso-arylporphyrin (43 μM) [ 56 ]. Nonetheless, it is still below the standards for cytotoxicity of plant extracts on mammalian cells [ 35 , 36 ].…”