1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents

1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents Full article

Journal

Molecules
, E-ISSN: 1420-3049

Output data

Year: 2020, Volume: 25, Number: 11, Article number : 2547, Pages count : DOI: 10.3390/molecules25112547

Tags

anthraquinones; Suzuki cross-coupling reaction; cytotoxicity; DNA binding

Authors

Sirazhetdinova Nafisa S. ¹ , Savelyev Victor A. ¹ , Frolova Tatyana S. ^3,2 , Baev Dmitry S. ¹ , Klimenko Lyubov S. ⁴ , Chernikov Ivan, V ⁵ , Oleshko Olga S. ³ , Sarojan Teresa A. ³ , Pokrovskii Andrey G. ³ , Shults Elvira E. ¹

Affiliations

1	(Данные Web of science) Russian Acad Sci, Siberian Branch, NN Vorozhtsov Novosibirsk Inst Organ Chem, Lab Med Chem, Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Fed Res Ctr Inst Cytol & Genet, Acad Lavrentyev Ave 10, Novosibirsk 630090, Russia
3	(Данные Web of science) Novosibirsk State Univ, Pirogova Str 1, Novosibirsk 630090, Russia
4	(Данные Web of science) Yugra State Univ, Khanty Mansiysk 628012, Russia
5	(Данные Web of science) Russian Acad Sci, Siberian Branch, Inst Chem Biol & Fundamental Med, Lavrentyev Ave 9, Novosibirsk 630090, Russia

A series of 1,2-, 1,4-disubstituted or 1,2,4-trisubstituted anthraquinone-based compounds was designed, synthesized, characterized and biologically evaluated for anticancer efficacy. 2- or 4-arylated 1-hydroxy-9,10-antraquinones (anthracene-9,10-diones) were prepared by Suzuki-Miyaura cross-coupling reaction of 1-hydroxy-2-bromoanthraquinone, 1-hydroxy-4-iodoanthraquinone or 1-hydroxy-2,4-dibromoanthraquinone with arylboronic acids. The cross-coupling reaction of 2,4-dibromo-9,10-anthraquinone with arylboronic acids provide a convenient approach to 2,4-bis arylated 1-hydroxyanthraquinones with a variety of aryl substituent in the 2 and 4 position. The cytotoxicity of new anthraquinone derivatives was evaluated using the conventional MTT assays. The data revealed that six of the aryl substituted compounds among the entire series 3, 15, 16, 25, 27, 28 were comparable potent with the commercially available reference drug doxorubicin on the human glioblastoma cells SNB-19, prostate cancer DU-145 or breast cancer cells MDA-MB-231 and were relatively safe towards human telomerase (h-TERT)immortalized lung fibroblasts cells. The results suggested that the in vitro antitumor activity of synthesized 2-aryl, 4-aryl- and 2,4-diaryl substituted 1-hydroxyanthraquinones depends on the nature of the substituent within the cyclic backbone. Docking interaction of 2-, 4-substituted and 2,4-disubstituted 1-hydroxyanthraquinones indicates intercalative mode of binding of compounds with DNA topoisomerase. The interaction with the DNA of 4-aryl-13, 15, 16 and 4-(furan-3-yl)-23 1-hydroxyanthraquinones was experimentally confirmed through a change in electroforetic mobility. Further experiments with 1-hydroxy-4-phenyl-anthraquinone 13 demonstrated that the compound induced cell cycle arrest at sub-G1 phase in DU-145 cells in the concentration 1.1 mu M, which is probably achieved by inducing apoptosis. 4-Arylsubstituted 1-hydroxyanthraquinones 13 and 16 induced the enhancement of DNA synthesis on SNB19 cell lines.

Sirazhetdinova N.S. , Savelyev V.A. , Frolova T.S. , Baev D.S. , Klimenko L.S. , Chernikov I.V. , Oleshko O.S. , Sarojan T.A. , Pokrovskii A.G. , Shults E.E.
1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents

Molecules. 2020. V.25. N11. 2547 . DOI: 10.3390/molecules25112547 WOS Scopus

Full text from publisher

Published online:

May 29, 2020

Web of science	WOS:000553858800084
Scopus	2-s2.0-85085909526
OpenAlex	W3028702062