Donor–acceptor (perylenethienyl)ethylenes as singlet oxygen photogenerating viral inhibitors

The development of broad-spectrum antiviral drugs effective against a wide variety of viruses is of significant practical importance. Perylene derivatives, which are pentacyclic aromatic hydrocarbons, have demonstrated strong antiviral activity. These compounds primarily act as membranoactive singlet oxygen photogenerators, disrupting virions and inhibiting fusion in enveloped viruses. Modifying the perylene core allows for chemical diversification of antiviral photosensitizers. Additionally, achieving a bathochromic shift in absorbance is crucial for the 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 antiviral activity against vesicular stomatitis virus (VSV), a representative enveloped virus. The incorporation of a thiophene unit into the molecule significantly enhanced both the quantum yield of singlet oxygen generation and the antiviral activity. These findings provide valuable insights into the relationship between the structure, spectral/photochemical properties, and biological activity of perylene-based photosensitizers.