Design and Synthesis of (2-<i>oxo</i>-1,2-Dihydroquinolin-4-yl)-1,2,3-triazole Derivatives via Click Reaction: Potential Apoptotic Antiproliferative Agents
Essmat M. El-Sheref,
Mohammed A. I. Elbastawesy,
Alan B. Brown,
Ahmed M. Shawky,
Hesham A. M. Gomaa,
Stefan Bräse,
Bahaa G. M. Youssif
Affiliations
Essmat M. El-Sheref
Chemistry Department, Faculty of Science, Minia University, El-Minia 61519, Egypt
Mohammed A. I. Elbastawesy
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
Alan B. Brown
Program in Chemistry, Florida Institute of Technology, 150 W University Blvd, Melbourne, FL 32901, USA
Ahmed M. Shawky
Science and Technology Unit (STU), Umm Al-Qura University, Makkah 21955, Saudi Arabia
Hesham A. M. Gomaa
Pharmacology Department, College of Pharmacy, Jouf University, Sakaka 72314, Saudi Arabia
Stefan Bräse
Institute of Organic Chemistry, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany
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 µM and 1.4 ± 0.2 µM 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.
