Discovery of novel thienoquinoline-2-carboxamide chalcone derivatives as antiproliferative EGFR tyrosine kinase inhibitors

Mahmoud S. Abdelbaset, Mohamed Abdel-Aziz, Mohamed Ramadan, Mostafa H. Abdelrahman, Bukhari Syed Nasir Abbas, Taha F.S. Ali, Gamal El Din A. Abuo-Rahma

Research output: Contribution to journalArticle

Abstract

Novel thienoquinoline carboxamide-chalcone derivatives were prepared via the cyclization of acylated chalcones and 2-mercaptoquinoline-3-carbaldehyde in DMF with K2CO3. Thienoquinolines 9a–f, h exhibited promising antiproliferative effect against all the tested cell lines and gave a significant activity as EGFR inhibitors, with IC50 values ranging from 0.5 and 3.2 µM, and compounds 9e and 9f being the most active of the series. They also showed better activity than Erlotinib against melanoma cancer cell line A375. Moreover, compound 9f influenced pre G1 apoptosis and cell cycle arrest at G2/M phase. The binding mode of the best EGFR inhibitor 9e in the EGFR active site revealed that the thienoquinoline ring occupied the ATP-binding site while the chalcone moiety is located in the allosteric site and is responsible for the enhanced activity of these compounds.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry
DOIs
Publication statusPublished - 1 Jan 2019
Externally publishedYes

Fingerprint

Chalcone
Protein-Tyrosine Kinases
Cells
Chalcones
Allosteric Site
Derivatives
G1 Phase Cell Cycle Checkpoints
Cell Line
G2 Phase
Cyclization
Cell Division
Inhibitory Concentration 50
Melanoma
Catalytic Domain
Adenosine Triphosphate
Binding Sites
Apoptosis
Neoplasms
Erlotinib Hydrochloride
potassium carbonate

Keywords

  • Antiproliferative
  • EGFR tyrosine kinase inhibitors
  • Molecular docking
  • Thienoquinoline

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Discovery of novel thienoquinoline-2-carboxamide chalcone derivatives as antiproliferative EGFR tyrosine kinase inhibitors. / Abdelbaset, Mahmoud S.; Abdel-Aziz, Mohamed; Ramadan, Mohamed; Abdelrahman, Mostafa H.; Syed Nasir Abbas, Bukhari; Ali, Taha F.S.; Abuo-Rahma, Gamal El Din A.

In: Bioorganic and Medicinal Chemistry, 01.01.2019.

Research output: Contribution to journalArticle

Abdelbaset, Mahmoud S. ; Abdel-Aziz, Mohamed ; Ramadan, Mohamed ; Abdelrahman, Mostafa H. ; Syed Nasir Abbas, Bukhari ; Ali, Taha F.S. ; Abuo-Rahma, Gamal El Din A. / Discovery of novel thienoquinoline-2-carboxamide chalcone derivatives as antiproliferative EGFR tyrosine kinase inhibitors. In: Bioorganic and Medicinal Chemistry. 2019.
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AU - Syed Nasir Abbas, Bukhari

AU - Ali, Taha F.S.

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