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

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 <i>N</i>-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using...

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Main Authors:	Dima A. Sabbah, Shaima’ E. Hasan, Reema Abu Khalaf, Sanaa K. Bardaweel, Rima Hajjo, Khalid M. Alqaisi, Kamal A. Sweidan, Aya M. Al-Zuheiri
Format:	Article
Language:	English
Published:	MDPI AG 2020-11-01
Series:	Molecules
Subjects:	anticancer colon cancer PI3Kα AKT docking quinolone-3-carboxamide
Online Access:	https://www.mdpi.com/1420-3049/25/22/5348

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spelling	doaj-c8ba3bf429cb4c129d3efef98ddfd2832020-11-25T04:03:50ZengMDPI AGMolecules1420-30492020-11-01255348534810.3390/molecules25225348Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer AgentsDima A. Sabbah0Shaima’ E. Hasan1Reema Abu Khalaf2Sanaa K. Bardaweel3Rima Hajjo4Khalid M. Alqaisi5Kamal A. Sweidan6Aya M. Al-Zuheiri7Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Pharmaceutical Sciences, School of Pharmacy, University of Jordan, Amman 11942, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanDepartment of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, JordanDepartment of Chemistry, The University of Jordan, Amman 11942, JordanDepartment of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, P.O. Box 130, Amman 11733, JordanThe 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 <i>N</i>-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (<sup>1</sup>H and <sup>13</sup>C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds <b>8</b> (IC<sub>50</sub> Caco-2 = 98 µM, IC<sub>50</sub> HCT-116 = 337 µM) and <b>16</b> (IC<sub>50</sub> Caco-2 = 13 µM, IC<sub>50</sub> HCT-116 = 240.2 µM). Results showed that compound <b>16 </b>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.https://www.mdpi.com/1420-3049/25/22/5348anticancercolon cancerPI3KαAKTdockingquinolone-3-carboxamide
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Dima A. Sabbah Shaima’ E. Hasan Reema Abu Khalaf Sanaa K. Bardaweel Rima Hajjo Khalid M. Alqaisi Kamal A. Sweidan Aya M. Al-Zuheiri
spellingShingle	Dima A. Sabbah Shaima’ E. Hasan Reema Abu Khalaf Sanaa K. Bardaweel Rima Hajjo Khalid M. Alqaisi Kamal A. Sweidan Aya M. Al-Zuheiri Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents Molecules anticancer colon cancer PI3Kα AKT docking quinolone-3-carboxamide
author_facet	Dima A. Sabbah Shaima’ E. Hasan Reema Abu Khalaf Sanaa K. Bardaweel Rima Hajjo Khalid M. Alqaisi Kamal A. Sweidan Aya M. Al-Zuheiri
author_sort	Dima A. Sabbah
title	Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents
title_short	Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents
title_full	Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents
title_fullStr	Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents
title_full_unstemmed	Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents
title_sort	molecular modeling, synthesis and biological evaluation of <i>n</i>-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamides as anticancer agents
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2020-11-01
description	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 <i>N</i>-phenyl-4-hydroxy-6-methyl-2-quinolone-3-carboxamide were synthesized and characterized using NMR (<sup>1</sup>H and <sup>13</sup>C) and HRMS. The derivatives displayed inhibitory activity against human epithelial colorectal adenocarcinoma (Caco-2) and human colon cancer (HCT-116) cell lines: compounds <b>8</b> (IC<sub>50</sub> Caco-2 = 98 µM, IC<sub>50</sub> HCT-116 = 337 µM) and <b>16</b> (IC<sub>50</sub> Caco-2 = 13 µM, IC<sub>50</sub> HCT-116 = 240.2 µM). Results showed that compound <b>16 </b>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.
topic	anticancer colon cancer PI3Kα AKT docking quinolone-3-carboxamide
url	https://www.mdpi.com/1420-3049/25/22/5348
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Molecular Modeling, Synthesis and Biological Evaluation of <i>N</i>-Phenyl-4-Hydroxy-6-Methyl-2-Quinolone-3-CarboxAmides as Anticancer Agents

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