Cascade Transformations of 1-R-Ethynyl-9,10-anthraquinones with Amidines: Expanding Access to Isoaporphinoid Alkaloids
Sergey Francevich Vasilevsky,
Ol’ga Leonidovna Krivenko,
Irina Vasilievna Sorokina,
Dmitry Sergeevich Baev,
Tatyana Genrikhovna Tolstikova,
Igor V. Alabugin
Affiliations
Sergey Francevich Vasilevsky
V.V. Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Ol’ga Leonidovna Krivenko
V.V. Voevodsky Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Irina Vasilievna Sorokina
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrent’eva, 630090 Novosibirsk, Russia
Dmitry Sergeevich Baev
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrent’eva, 630090 Novosibirsk, Russia
Tatyana Genrikhovna Tolstikova
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Acad. Lavrent’eva, 630090 Novosibirsk, Russia
Igor V. Alabugin
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306, USA
The interaction of acetamidine and phenylamidine with peri-R-ethynyl-9,10-anthraquinones in refluxing n-butanol leads to the formation of cascade transformations products: addition/elimination/cyclization―2-R-7H-dibenzo[de,h]quinolin-7-ones and(or) 2-R-3-aroyl-7H-dibenzo[de,h]quinolin-7-ones. The anti-inflammatory and antitumor properties of the new 2-R-7H-dibenzo[de,h]quinolin-7-ones were investigated in vivo, in vitro, and in silico. The synthesized compounds exhibit high anti-inflammatory activity at dose 20 mg/kg (intraperitoneal injection) in the models of exudative (histamine-induced) and immunogenic (concanavalin A-induced) inflammation. Molecular docking data demonstrate that quinolinones can potentially intercalate into DNA similarly to the antitumor drug doxorubicin.
