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STRUCTURE‐ACTIVITY STUDIES OF PHOTOACTIVATED ANTIVIRAL AND CYTOTOXIC TRICYCLIC THIOPHENES
Author(s) -
Marles Robin J.,
Hudson James B.,
Graham Elizabeth A.,
SoucyBreau Chantal,
Morand Peter,
Compadre R. Lilia,
Compadre Cesar M.,
Towers G. H. Neil,
Arnason J. Thor
Publication year - 1992
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1992.tb02191.x
Subject(s) - phototoxicity , tricyclic , cytotoxic t cell , chemistry , sindbis virus , thiophene , structure–activity relationship , singlet oxygen , cytotoxicity , stereochemistry , pharmacology , biochemistry , in vitro , biology , organic chemistry , oxygen , rna , gene
— The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, α‐terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, α‐terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02–40 μ M . 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.