N -Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-CarboxAmides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents

N -Phenyl-6-Chloro-4-Hydroxy-2-Quinolone-3-CarboxAmides: Molecular Docking, Synthesis, and Biological Investigation as Anticancer Agents

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 derivat...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Vol. 26; no. 1; p. 73
Main Authors: Sabbah, Dima A, Haroon, Rawan A, Bardaweel, Sanaa K, Hajjo, Rima, Sweidan, Kamal
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 25-12-2020
MDPI
Subjects:
1-Phosphatidylinositol 3-kinase
Acids
Adenocarcinoma
AKT
anticancer
Binding sites
Cancer
Carcinogenesis
Carcinogens
Cell growth
Colon
colon cancer
Colorectal cancer
Design
docking
Drug development
Hydrocarbons
Investigations
Kinases
Ligands
Mass spectra
Molecular docking
Permeability
PI3Kα
quinolone-3-carboxamide
Radiation
Tumor cell lines
quinolone-3-carboxamide
docking
PI3Kα
AKT
colon cancer
anticancer
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Summary: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 -phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamide were synthesized and characterized using FT-IR, NMR ( H and C), and high-resolution mass spectra (HRMS). The series exhibited distinct antiproliferative activity (IC µM) against human epithelial colorectal adenocarcinoma (Caco-2) and colon carcinoma (HCT-116) cell lines, respectively: compounds (37.4, 8.9 µM), (50.9, 3.3 µM), (17.0, 5.3 µM), and (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.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules26010073