title: Structure-activity studies of photoactivated antiviral and cytotoxic tricyclic thiophenes.
abstract: The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, alpha-terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, alpha-terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02-40 microM. In the absence of near UV irradiation, only one analogue had antiviral activity and five were cytotoxic. The most active analogues were those containing carboxylic acid, hydroxyl, or cyano substituents. Quantitative structure-activity relationship analysis of thiophene phototoxicity suggested that the rate of singlet oxygen production is the primary determinant of antiviral and cytotoxic activities. For phototoxicity against murine cytomegalovirus, a significant role for hydrophobicity was also demonstrated. Tricyclic thiophenes show significant potential for photochemotherapy of viral infections and cancer, and further evaluation in animal models is recommended.
authors.affiliation: Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada.
authors.forename: R J
authors.initials: RJ
authors.lastname: Marles
authors.forename: J B
authors.initials: JB
authors.lastname: Hudson
authors.forename: E A
authors.initials: EA
authors.lastname: Graham
authors.forename: C
authors.initials: C
authors.lastname: Soucy-Breau
authors.forename: P
authors.initials: P
authors.lastname: Morand
authors.forename: R L
authors.initials: RL
authors.lastname: Compadre
authors.forename: C M
authors.initials: CM
authors.lastname: Compadre
authors.forename: G H
authors.initials: GH
authors.lastname: Towers
authors.forename: J T
authors.initials: JT
authors.lastname: Arnason
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003587:Cytomegalovirus / Q000187:drug effects* / Q000528:radiation effects; D012515:Mast-Cell Sarcoma; D051379:Mice; D012845:Sindbis Virus / Q000187:drug effects* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D013876:Thiophenes