Molecular Modeling, Synthesis and Biological Evaluation of N-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents

Molecules

KamalA. Sweidan¹  KhalidM. Alqaisi²  SanaaK. Bardaweel³  Rima Hajjo⁴  Shaima’E. Hasan⁴  Reema Abu Khalaf⁴  DimaA. Sabbah⁴  AyaM. Al-Zuheiri⁴ 

[1] Department of Chemistry, The University of Jordan, Amman 11942, Jordan;Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan;Department of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, Jordan;Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, Jordan;

关键词: anticancer;    colon cancer;    PI3Kα;    AKT;    docking;    quinolone-3-carboxamide;   

DOI  :  10.3390/molecules25225348

来源: DOAJ

【 摘 要 】

The emergence of phosphatidylinositol 3-kinase (PI3Kα) in cancer development has accentuated its significance as a potential target for anticancer drug design. Twenty one derivatives of N-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (¹H and ¹³C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds 8 (IC₅₀ Caco-2 = 98 µM, IC₅₀ HCT-116 = 337 µM) and 16 (IC₅₀ Caco-2 = 13 µM, IC₅₀ HCT-116 = 240.2 µM). Results showed that compound 16 significantly affected the gene encoding AKT, BAD, and PI3K. The induced-fit docking (IFD) studies against PI3Kα demonstrated that the scaffold accommodates the kinase domains and forms H-bonds with significant binding residues.

【 授权许可】

Unknown