Discovery of Novel Quinoline-Based Analogues of Combretastatin A-4 as Tubulin Polymerization Inhibitors with Apoptosis Inducing Activity and Potent Anticancer Effect

Faculty Pharmacy Year: 2021
Type of Publication: ZU Hosted Pages: 802–818
Authors:
Zakareyah Kamel Abdelsamie
Journal: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY Taylor & Francis Group Volume: 36
Keywords : Discovery , Novel Quinoline-Based Analogues , 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 polymerization 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.
    
     
 
       

Author Related Publications

  • Zakareyah Kamel Abdelsamie, "Regioselective hydroxysulphenylation of derivatives of allylic alcohols and amines.", Tetrahedron Letters, 1986 More
  • Zakareyah Kamel Abdelsamie, "New routes to heterocycles via sulphenylation of unsaturated amides", Tetrahedron Letters, 1987 More
  • Zakareyah Kamel Abdelsamie, "Trifluoroacetoxysulphenylation of unsaturated nitriles as a route to lactones", Tetrahedron Letters, 1986 More
  • Zakareyah Kamel Abdelsamie, "Synthesis of certain s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives of pharmaceutical interest", Eygpt J. Pharm. Sci, 1987 More
  • Zakareyah Kamel Abdelsamie, "Synthesis and biological activity of some novel triazolothiadiazines", Eygpt J. Pharm. Sci, 1988 More

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