N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides: Molecular Docking,Synthesis, and Biological Investigation as Anticancer Agents |
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Authors: | Dima A Sabbah Rawan A Haroon Sanaa K Bardaweel Rima Hajjo Kamal Sweidan |
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Institution: | 1.Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan; (R.A.H.); (R.H.);2.Department of Pharmaceutical Sciences, School of Pharmacy, The University of Jordan, Amman 11942, Jordan;3.Department of Chemistry, The University of Jordan, Amman 11942, Jordan; |
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Abstract: | Cancer is a multifactorial disease and the second leading cause of death worldwide. Diverse factors induce carcinogenesis, such as diet, smoking, radiation, and genetic defects. The phosphatidylinositol 3-kinase (PI3Kα) has emerged as an attractive target for anticancer drug design. Eighteen derivatives of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR (1H and 13C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC50 µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds 16 (37.4, 8.9 µM), 18 (50.9, 3.3 µM), 19 (17.0, 5.3 µM), and 21 (18.9, 4.9 µM). The induced-fit docking (IFD) studies against PI3Kαs showed that the derivatives occupy the PI3Kα binding site and engage with key binding residues. |
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Keywords: | anticancer colon cancer PI3Kα AKT docking quinolone-3-carboxamide |
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