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

Abstract

Anthraquinones are of signi cant interest due to their biological activity, coloring properties and synthetic applications. Here, we describe a mild and convenient method for modi cation of 1-ethynyl-4hydroxyanthraquinone that was obtained from the Sonogashira reaction of 1-hydroxy-4iodoanthraquinone with alkynes. The copper(I) catalyzed one-pot three component reaction (A 3 -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 in uence 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, and 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.

Journey of anthraquinones as anticancer agents – a systematic review of recent literature

“…Further, the molecular binding studies of the synthesized compounds towards DNA G-quadruplex revealed that almost all the derivatives showed good binding affinities towards DNA motifs. 126 In yet another research study, 2,6-disubstituted amido anthracene-9,10-dione dimeric distamycin derivatives were designed and synthesized. Among all the synthesized derivatives, the disubstituted anthraquinone with tri- N -methylpyrrole side chain (ANTP) was found to be more promising and exhibited good activity towards c-Myc G-quadruplex DNA with a binding affinity of 3.8 ± 0.01 × 10 6 M −1 .…”