Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives Full article

Journal

Medicinal Chemistry Research
ISSN: 1054-2523 , E-ISSN: 1554-8120

Output data

Year: 2021, Volume: 30, Pages: 1541–1556 Pages count : DOI: 10.1007/s00044-021-02754-1

Tags

A3-coupling; Anthraquinone; Anti-cancer; DNA; G-quadruplex; Sonogashira reaction

Authors

Sirazhetdinova N.S. ¹ , Savelyev V.A. ¹ , Baev D.S. ¹ , Golubeva T.S. ² , Klimenko L.S. ³ , Tolstikova T.G. ¹ , Ganbaatar J. ⁴ , Shults E.E. ¹

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, Lavrentyev Ave, 9, Novosibirsk, 630090, Russian Federation
2	The Federal Research Center Institute of Cytology and Genetics, Acad. Lavrentyev Ave., 10, Novosibirsk, 630090, Russian Federation
3	Yugra State University, Khanty-Mansiysk, 628012, Russian Federation
4	Institute of Chemistry and Chemical Technology, Mongolian Academy of Sciences, Ulan-Bator, Mongolia

Anthraquinones are of significant interest due to their biological activity, coloring properties, and synthetic applications. Here, we describe a mild and convenient method for modification of 1-ethynyl-4-hydroxyanthraquinone that was obtained from the Sonogashira cross-coupling reaction of 1-hydroxy-4-iodoanthraquinone with alkynes. The copper(I) catalyzed one-pot three-component reaction (A3-coupling) of the new 1-ethynyl-4-hydroxyanthraquinone with secondary amines and formaldehyde was the main approach for the synthesis of nitrogen-substituted 1-[3-(amino)prop-1-ynyl]-4-hydroxyanthraquinones. The influence of different substituents in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was assessed using the conventional MTT assay. Among all compounds synthesized, anthraquinone-propargylamine derivatives 28, 29, 30, and 34 possess the most promising cytotoxic potential towards glioblastoma cancer cells; compounds 14 and 19 shown selectivity towards the prostate cancer cells DU-145, and 18, 24 — on breast cancer cell line MCF-7. The grown inhibition on these cancer cells by compounds 18 and 24 was comparable to those of standard drug Doxorubicin. Molecular modeling of new anthraquinone derivatives in DNA G-quadruplex binding sites was performed to help understand the observed SAR trends. [Figure not available: see fulltext.] © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Sirazhetdinova N.S. , Savelyev V.A. , Baev D.S. , Golubeva T.S. , Klimenko L.S. , Tolstikova T.G. , Ganbaatar J. , Shults E.E.
Synthesis, characterization and anticancer evaluation of nitrogen-substituted 1-(3-aminoprop-1-ynyl)-4-hydroxyanthraquinone derivatives

Medicinal Chemistry Research. 2021. V.30. P.1541–1556. DOI: 10.1007/s00044-021-02754-1 WOS Scopus РИНЦ

Full text from publisher

Published online:	Jun 15, 2021
Published print:	Aug 1, 2021

Web of science	WOS:000661760700002
Scopus	2-s2.0-85107942107
Elibrary	46819638
OpenAlex	W4237078073