Design, synthesis and anticancer evaluation of naphthalen-1-yloxyacetamide derivatives against MCF-7 cells

Abstract

Herein, a set of naphthalen-1-yloxyacetamide-tethered 2,3-disubstituted acrylamide conjugates was synthesized in a good yield via the reaction of naphthalene-1-yloxyacetohydrazide and an equimolar amount of respective ethyl 2,3-disubstituted acrylate ester in pure ethanol with a catalytic base of fused sodium acetate. All conjugates were assessed for their anti-proliferative activity against the MCF-7 Br Ca cell line. The results found that conjugate 5d with 3-(4-methoxyphenyl)-2-phenylacrylamide attached to the naphthalen-1-yloxyacetamide moiety demonstrated potent cytotoxic activity against the investigated MCF-7 Br Ca cells. Thereafter, compounds 5c, 5d, and 5e were subsequently evaluated for their aromatase inhibitory activity. Moreover, the representative promising conjugate in cytotoxic and aromatase inhibition assays was tested to investigate its impact on the cell cycle analysis and apoptosis promotion with the aim to get more insight into the antitumor mechanism of action of the target naphthalen-1-yloxyacetamide-acrylamide conjugates. In the examined MCF-7 cells, compound 5d heightened cell cycle arrest during the G1 phase and provoked cellular apoptosis. Furthermore, compound 5d increased the apoptosis percentage via the expressive downregulation of the anti-apoptotic protein Bcl-2 and the upregulation of Bax and caspase 9 levels relative to untreated groups.