Donor-Acceptor (Perylenethienyl)Ethylenes as Singlet Oxygen-Photogenerating Viral Inhibitors

The development of broad-spectrum antiviral drugs effective against a wide range of viruses is of significant practical importance. Derivatives of perylene, a pentacyclic aromatic hydrocarbon, demonstrate pronounced antiviral activity. These compounds act primarily as membrane-active singlet oxygen photogenerators, disrupting virions and inhibiting their fusion with the host cell membrane. Modification of the perylene core allows for chemical diversification of antiviral photosensitizers. Additionally, achieving a bathochromic shift of the absorption band is crucial for effective treatment of superficial lesions, as it facilitates deeper tissue penetration of therapeutic light. In this work, donor-acceptor perylenylethylenes and (perylenethienyl)ethylenes were synthesized and evaluated for their spectral properties, singlet oxygen photogeneration, and inhibitory activity against vesicular stomatitis virus (VSV), a representative enveloped virus. Incorporation of a thiophene moiety into the molecule significantly enhanced both the singlet oxygen generation ability and the antiviral activity. These findings provide useful insights into the relationship between the structure, spectral/photochemical properties, and biological activity of perylene-based photosensitizers.