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

Abstract

The development of broad-spectrum antiviral drugs effective against a wide variety of viruses is of significant practical importance. Derivatives of perylene, a pentacyclic aromatic hydrocarbon, demonstrate pronounced antiviral activity. These compounds primarily act as membrane-active singlet oxygen photogenerators, disrupting virions and inhibiting their fusion with a host cell membrane. Modifying the perylene core allows for chemical diversification of antiviral photosensitizers. Additionally, achieving a bathochromic shift in absorbance 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 inhibition activity against vesicular stomatitis virus (VSV), a representative enveloped virus. The incorporation of a thiophene unit 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.