title: Tyrosyl-DNA Phosphodiesterase 1 Inhibitors: Usnic Acid Enamines Enhance the Cytotoxic Effect of Camptothecin.
abstract: Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a repair enzyme for stalled DNA-topoisomerase 1 (Top1) cleavage complexes and other 3'-end DNA lesions. TDP1 is a perspective target for anticancer therapy based on Top1-poison-mediated DNA damage. Several novel usnic acid derivatives with an enamine moiety have been synthesized and tested as inhibitors of TDP1. The enamines of usnic acid showed IC50values in the range of 0.16 to 2.0 μM. These compounds revealed moderate cytotoxicity against human tumor MCF-7 cells. These new compounds enhanced the cytotoxicity of the established Top1 poison camptothecin by an order of magnitude.
authors.affiliation: Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zakharenko
authors.affiliation: N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.
authors.forename: Olga
authors.initials: O
authors.lastname: Luzina
authors.affiliation: Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.|Novosibirsk State University , Novosibirsk, 630090, Russian Federation.
authors.forename: Olga
authors.initials: O
authors.lastname: Koval
authors.forename: Dmitry
authors.initials: D
authors.lastname: Nilov
authors.forename: Irina
authors.initials: I
authors.lastname: Gushchina
authors.affiliation: Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Dyrkheeva
authors.forename: Vytas
authors.initials: V
authors.lastname: Švedas
authors.affiliation: N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.|Novosibirsk State University , Novosibirsk, 630090, Russian Federation.
authors.forename: Nariman
authors.initials: N
authors.lastname: Salakhutdinov
authors.affiliation: Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences , Novosibirsk, 630090, Russian Federation.|Novosibirsk State University , Novosibirsk, 630090, Russian Federation.
authors.forename: Olga
authors.initials: O
authors.lastname: Lavrik
mesh_terms: D001572:Benzofurans / Q000378:metabolism / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D010726:Phosphodiesterase Inhibitors; C073339:usnic acid; D010727:Phosphoric Diester Hydrolases; C122147:tyrosyl-DNA phosphodiesterase; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D002166:Camptothecin