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Design and Synthesis of (2-oxo-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents

Research Authors
Essmat M. El-Sheref, Mohammed A. I. Elbastawesy, Alan B. Brown, Ahmed M. Shawky, Hesham A. M. Gomaa, Stefan Bräse, Bahaa G. M. Youssif
Research Date
Research Journal
Molecules
Research Publisher
MDPI
Research Rank
Q2
Research Vol
26
Research Website
https://doi.org/10.3390/ molecules26226798
Research Year
2021
Research_Pages
6798
Research Abstract

A mild and versatile method based on Cu-catalyzed [2+3] cycloaddition (Huisgen-Meldal-
Sharpless reaction) was developed to tether 3,3’-((4-(prop-2-yn-1-yloxy)phenyl)methylene)bis(4-
hydroxyquinolin-2(1H)-ones) with 4-azido-2-quinolones in good yields. This methodology allowed
attaching three quinolone molecules via a triazole linker with the proposed mechanism. The products
are interesting precursors for their anti-proliferative activity. Compound 8g was the most active one,
achieving IC50 = 1.2 0.2 M and 1.4 0.2 M against MCF-7 and Panc-1 cell lines, respectively.
Moreover, cell cycle analysis of cells MCF-7 treated with 8g showed cell cycle arrest at the G2/M
phase (supported by Caspase-3,8,9, Cytochrome C, BAX, and Bcl-2 studies). Additionally, significant
pro-apoptotic activity is indicated by annexin V-FITC staining.