A series of novel N-substituted 3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-carboxy- lic acid derivatives were synthesized and evaluated for their biological activities. Among all synthesized target compounds, 13d exhibited the most potent antiproliferative activity against HeLa, SMMC-7721, K562 cell line (IC50 = 0.126 μM, 0.071 μM, 0.164 μM, respectively). Furthermore, compound 13d inhibited tubulin polymerization (IC50 = 3.97 μM), arrested cell cycle at the G2/M phase and induced apoptosis. The binding mode at the colchicine binding site was also probed. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
European Journal of Medicinal Chemistry – Elsevier
Published: Jan 1, 2018
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