title: A novel tetrahydrobenzoangelicin with dark and photo biological activity.
abstract: The synthesis of 8,9,10,11-tetrahydro-5-(3-dimethylaminopropoxy)-4-methylbenzofuro[2,3-h]coumarin (5) is described. The new compound showed the ability to inhibit cell growth both upon UVA irradiation and in the dark. The investigation on the mechanism of action highlighted the capacity of 5 to covalently photoadd to thymine, as demonstrated by the isolation and characterization of the 4',5'-monoadduct. Furthermore, in the ground state 5 interferes with the topoisomerase II relaxation activity, suggesting that this enzyme could constitute a molecular target responsible for the dark antiproliferative effect.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy. lisa.dallavia@unipd.it
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
authors.forename: Ornella
authors.initials: O
authors.lastname: Gia
authors.forename: Sergio
authors.initials: S
authors.lastname: Caffieri
authors.forename: Aída N
authors.initials: AN
authors.lastname: García-Argáez
authors.forename: Elías
authors.initials: E
authors.lastname: Quezada
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D018736:DNA Adducts; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D011564:Furocoumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010778:Photochemotherapy; D013941:Thymine / Q000737:chemistry; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: C575347:8,9,10,11-tetrahydro-5-(3-dimethylaminopropoxy)-4-methylbenzofuro(2,3-h)coumarin; D000970:Antineoplastic Agents; D018736:DNA Adducts; D011564:Furocoumarins; D059005:Topoisomerase II Inhibitors; D004247:DNA; D004250:DNA Topoisomerases, Type II; D013941:Thymine