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
    
     
 
       

Author Related Publications

  • Tarek Mohamed Salah Rashad, "Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors", mdpi, 2022 More
  • Tarek Mohamed Salah Rashad, "New Multi-Targeted Antiproliferative Agents: Design and Synthesis of IC261-Based Oxindoles as Potential Tubulin, CK1 and EGFR Inhibitors", mdpi, 2021 More
  • Tarek Mohamed Salah Rashad, "Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction", Taylor & Francis Group, 2021 More
  • Tarek Mohamed Salah Rashad, "Novel 1,2,4-triazine-quinoline hybrids: The privileged scaffolds as potent multi-target inhibitors of LPS-induced inflammatory response via dual COX-2 and 15-LOX inhibition", ELSEVIER, 2021 More
  • Tarek Mohamed Salah Rashad, "Design, synthesis and pharmacological screening of novel renoprotective methionine-based peptidomimetics: Amelioration of cisplatin-induced nephrotoxicity", ELSEVIER, 2021 More

Department Related Publications

  • Amany Mohamed Mohamed Elmahmoudy Sanger, "Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors", mdpi, 2022 More
  • Tarek Mohamed Salah Rashad, "Uracil as a Zn-Binding Bioisostere of the Allergic Benzenesulfonamide in the Design of Quinoline–Uracil Hybrids as Anticancer Carbonic Anhydrase Inhibitors", mdpi, 2022 More
  • Amany Mohamed Mohamed Elmahmoudy Sanger, "Synthesis, Antibacterial Evaluation, and Computational Studies of a Diverse Set of Linezolid Conjugates", mdpi, 2022 More
  • Tarek Mohamed Salah Rashad, "New Multi-Targeted Antiproliferative Agents: Design and Synthesis of IC261-Based Oxindoles as Potential Tubulin, CK1 and EGFR Inhibitors", mdpi, 2021 More
  • Tarek Mohamed Salah Rashad, "Novel chalcone/aryl carboximidamide hybrids as potent anti-inflammatory via inhibition of prostaglandin E2 and inducible NO synthase activities: design, synthesis, molecular docking studies and ADMET prediction", Taylor & Francis Group, 2021 More
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