Antiviral properties of psoralen derivatives: a biological and physico-chemical investigation.
Two isomeric psoralen derivatives (I and II in Fig. 1) bearing charged side chains, have been tested for activity against Herpes Simplex Virus type 1 (HSV-1) in the absence of u.v. irradiation. Striking differences have been observed both in antiviral and cytotoxic activity for the examined compounds, I being appreciably more effective. Metabolic and biochemical studies, as well as physico-chemical measurements indicate DNA as the major target. The different biological behaviour can be fully explained in terms of a modified affinity of the drugs toward DNA. The molecular basis for these findings probably stems from slightly different intercalation geometries, as shown by chiroptical studies. Comparable binding affinities for viral and cellular DNA fully account for lack of selective toxicity found in vivo. The present approach is proposed as a tool for the investigation of structure-function relationships in drug models.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D011564:Furocoumarins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014316:Tritium; D014764:Viral Proteins / Q000096:biosynthesis
D000998:Antiviral Agents; D011564:Furocoumarins; D014764:Viral Proteins; D014316:Tritium; D004247:DNA