Potent Quinoline-Containing Combretastatin A-4 Analogues: Design, Synthesis, Antiproliferative, and Anti-Tubulin Activity

• DOI: 10.3390/ph13110393
• Publication Date: 2020-11-16T16:04:20Z
• Authors: Tarek S. Ibrahim; Mohamed M. Hawwas; Azizah M. Malebari; Ehab S. Taher; Abdelsattar M. Omar; Niamh M. O'Boyle; Eavan McLoughlin; Zakaria K. Abdel-...; Yaseen A. M. M. E...
• Keywords: Combretastatin; Quinoline; Hydrazone

A novel series of quinoline derivatives combretastatin A-4 incorporating rigid hydrazone and a cyclic oxadiazole linkers were synthesized have demonstrated potent tubulin polymerization inhibitory properties. Many these shown significant antiproliferative activities in the submicromolar range. The most compound, 19h, superior IC50 values ranging from 0.02 to 0.04 µM against four cancer cell lines while maintaining low cytotoxicity MCF-10A non-cancer cells, thereby suggesting 19h’s selectivity towards proliferating cells. In addition inhibition, 19h caused cycle arrest MCF-7 cells at G2/M phase induced apoptosis. Collectively, findings indicate that holds potential for further investigation as chemotherapeutic agent targeting tubulin.