Synthesis, Characterization and Anticancer Evaluation of Nitrogen Substituted 1-(3-Aminoprop-1-ynyl)-4-Hydroxyanthraquinone Derivatives
| Autor: | Elvira E. Shults, Tatyana S. Golubeva, Lyubov S. Klimenko, Dmitry S. Baev, Victor A. Savelyev, Nafisa S. Sirazhetdinova, Tatyana G. Tolstikova, Jamsranjav Ganbaatar |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
010405 organic chemistry
Chemistry Sonogashira coupling Biological activity Hydroxyanthraquinone 01 natural sciences Combinatorial chemistry 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry.chemical_compound Anthraquinones Cancer cell Amine gas treating MTT assay Cytotoxicity |
| Popis: | 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 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 substituent in the amine on reaction rate and yield has been evaluated. The cytotoxicity of 1-ethynyl-4-hydroxyanthraquinones was evaluated using the conventional MTT assay. Among all the compounds synthesized, anthraquinone-propargylamine derivatives 28, 29, 30 and 34 possess most promising cytotoxic potential towards glioblastoma cancer cells; compounds 14 and 19 shown selectivity towards the prostate cancer cells DU-145, and 18, and 24 – towards breast cancer cells MCF-7. The grown inhibition on these cancer cells of 18 and 24 was comparable to those of standard drug Doxorubicin. Molecular modeling of new compounds in DNA G-quadruplex binding site was performed to help understand the observed SAR trends. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|