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

Dima A. Sabbah,Rima Hajjo,Kamal Sweidan,Sanaa K. Bardaweel,Rawan A. Haroon

doi:10.3390/molecules26010073

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.

Highlights

The emergence of cancer cases continues to rise worldwide
Applying pharmacophore modeling and database screening against the national cancer institute (NCI) database [17], we previously revealed N-benzyl-4-hydroxy-2-quinolone
Thin-layer chromatography (TLC) application was recruited to monitor the reaction progress; the absence of a spot belonging to 3 highlighted the completeness of the reaction

Summary

Introduction

The emergence of cancer cases continues to rise worldwide. A group of diseases, is considered a prevalent health problem and cause of death. Cancer is uncontrolled cell proliferation accompanied with invasion to other body organs [1]. Multiple factors induce cancer occurrence, such as smoking, diet, radiation, viral infections, and genetic disorders [2,3,4,5]. Phosphatidylinositol 3-kinases (PI3Ks) catalyze the phosphorylation of phosphatidylinositol on the 3-OH group of inositol ring generating phosphatidylinositol. PIP3 invoke downstream effectors and signaling proteins such as protein kinase B (AKT) inducing cell growth and multiplication [6,7]

Methods

Results

Conclusion