Synthesis and biological evaluation of some hybrid 2-quinolinone derivatives containing cinnamic acid as anti-breast cancer drugs

S B Bakare

doi:10.4314/bcse.v35i3.7

Abstract

ABSTRACT. A new series of hybrid 2-quinolinone derivatives were synthesized by using 7-hydroxy-4-methyl-1-amino-quinolin-2-one (2) and cinnamic acid. Hybrid halogenated 2-quinolinone derivatives (3-(7-hydroxy-4-methyl-3,6,8-tribromo-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (4) and 3-(7-acetoxy-4-methyl-3,6,8-tribromo-2-oxo-1H-quinolin-1-ylamino)-3-phenyl acrylic acid (7)) were prepared via the halogenation of 3-(7-hydroxy-4-methyl-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (3) with bromine to give compound 4 with acetic anhydride led to the formation of hydride halogenated 2-quinolinone derivative (7). All the synthesized hybrid 2-quinolinone and hybrid halogenated 2-quinolinone derivatives were tested for their cytotoxicity against MCF-7 cell line. DNA flow cytometric analysis of compounds 3 showed cell cycle arrest at G2/M phase with concomitant increase of cells in apoptotic phase. Dual annexin-V/propidium iodide staining assay of compound 3 revealed that, the selected molecule increases the apoptosis of MCF-7 cells more than control.  KEY WORDS: Quinolinone, Hybrid, Cinnamic acid, Apoptosis, MCF-7 cells  Bull. Chem. Soc. Ethiop. 2021, 35(3), 551-564. DOI: https://dx.doi.org/10.4314/bcse.v35i3.7

Highlights

Several authors have reported that numerous quinolinone derivatives showed strong antiproliferative activity and induce apoptosis in various cancer cell lines [1, 2]
Treatment of compound 1 with hydrazine hydrate in pyridine under reflux led to the formation of 7-hydroxy-4-methyl-2-oxo-1-aminoquinoline (2) according to literature method [31], as a key starting material
Structure of compound 3 was confirmed via its transformation into 3-(7-hydroxy-4-methyl3,6,8-tribromo-2-oxoquinolin-1-ylamino)-3-phenyl acrylic acid (4) by bromination of compound 3 which contain free hydroxyl and methyl group in positions 3 and 7, led to the substitution reaction in this compound (3) at position 3,6 and 8 with bromine

Summary

Introduction

Several authors have reported that numerous quinolinone derivatives showed strong antiproliferative activity and induce apoptosis in various cancer cell lines [1, 2]. Acetylation of compound 3 with acetic anhydride under reflux was expected to give structure 5, but only 7-acetoxy-4-methyl-2-oxo-1H-quinoline (6, known) was yielded, via the elimination of cinnamic acid molecule from compound 3. While the acetylation of compound 4 with acetic anhydride under boiling led to the expected structure of 3-(7-acetoxy-4-methyl-3,6,8-tribromo-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (7) without elimination of cinnamic acid molecule from the compound 4.

Results

Conclusion