Discovery of novel quinoline-based analogues of combretastatin A-4 as tubulin polymerisation inhibitors with apoptosis inducing activity and potent anticancer effect

Faculty Pharmacy Year: 2021
Type of Publication: ZU Hosted Pages: 802-818
Authors:
Tarek Mohamed Salah Rashad
Journal: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY Taylor & Francis Group Volume: 1
Keywords : Discovery , novel quinoline-based analogues of combretastatin , , tubulin    
Abstract:
A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC50 ranging from 0.010 to 0.042 mM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G2/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer
    
     
 
       

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Department Related Publications

  • Etedaal Hassan Mohamed Abdulaal, "18. In situ annelation of enaminones by reaction with methyleneiminium intermediates", لايوجد, 1900 More
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