Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors

Mahmoud S. Abdelbaset, Gamal El Din A. Abuo-Rahma, Mostafa H. Abdelrahman, Mohamed Ramadan, Bahaa G.M. Youssif, Bukhari Syed Nasir Abbas, Mamdouh F.A. Mohamed, Mohamed Abdel-Aziz

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A novel quinolinyl pyrrolone and quinolinyl pyridazinone derivatives has been synthesized and characterized using different spectroscopic and elemental analysis techniques. Most of the target compounds displayed promising antiproliferative activity; In general, the pyrrolone derivatives 4a-f exhibited higher antiproliferative activity than their corresponding pyridazinone. The pyrrolone 4f showed outstanding antiproliferative activity with moderate selectivity against CNS and renal cancer with selectivity ratio of 3.49 and 3.56, respectively. Compound 4e and 5d experienced tubulin polymerization inhibitory activity comparable to that of vincristine while 4c, 4e and 4d showed good BRAF kinase inhibition compared to Erlotinib. Docking of compound 4e into colchicine binding site and biological assay results revealed that these compounds act mainly through tubulin polymerization inhibitory mechanism and can exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase.

Original languageEnglish
Pages (from-to)151-163
Number of pages13
JournalBioorganic Chemistry
Volume80
DOIs
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Fingerprint

Tubulin Modulators
Tubulin
Scaffolds
Polymerization
Proto-Oncogene Proteins B-raf
Derivatives
G1 Phase Cell Cycle Checkpoints
Spectroscopic analysis
Kidney Neoplasms
G2 Phase
Colchicine
Vincristine
Biological Assay
Cell Division
Assays
Binding Sites
Cells
Apoptosis
Chemical analysis
quinoline

Keywords

  • Antiproliferative
  • BRAF Kinase
  • Pyridazin-3(2H)-ones
  • Pyrrol-2(3H)-ones
  • Quinoline
  • Tubulin polymerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors. / Abdelbaset, Mahmoud S.; Abuo-Rahma, Gamal El Din A.; Abdelrahman, Mostafa H.; Ramadan, Mohamed; Youssif, Bahaa G.M.; Syed Nasir Abbas, Bukhari; Mohamed, Mamdouh F.A.; Abdel-Aziz, Mohamed.

In: Bioorganic Chemistry, Vol. 80, 01.10.2018, p. 151-163.

Research output: Contribution to journalArticle

Abdelbaset, Mahmoud S. ; Abuo-Rahma, Gamal El Din A. ; Abdelrahman, Mostafa H. ; Ramadan, Mohamed ; Youssif, Bahaa G.M. ; Syed Nasir Abbas, Bukhari ; Mohamed, Mamdouh F.A. ; Abdel-Aziz, Mohamed. / Novel pyrrol-2(3H)-ones and pyridazin-3(2H)-ones carrying quinoline scaffold as anti-proliferative tubulin polymerization inhibitors. In: Bioorganic Chemistry. 2018 ; Vol. 80. pp. 151-163.
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