Synthesis and biological evaluation of quinoxaline derivatives as tubulin polymerization inhibitors that elevate intracellular ROS and triggers apoptosis via mitochondrial pathway

Abstract

A series of novel quinoxaline derivatives were synthesized and evaluated for their antiproliferative activity in three human cancer cell lines. Compound 12 exhibited the most potent antiproliferative activity with IC50 in the range of 0.19–0.51 μM. The compound inhibited tubulin polymerization and disrupted the microtubule network, leading to G2/M phase arrest. Furthermore, compound 12 induced ROS production and malfunction of mitochondrial membrane potential. Compound 12 led to cancer cells apoptosis in a dose‐dependent manner. Western blot analysis showed that compound 12 induced up‐regulation of p21 and affected the expression of cell cycle‐related proteins. The binding mode was also probed by molecular docking.

Synthesis of 7-amino-6-halogeno-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: a way forward for targeting hypoxia and drug resistance of cancer cells

“…Quinoxaline derivatives are active inducers of tumor cell death, as discussed in several papers. [29][30][31][32] For instance, quinoxaline dioxide DCQ causes the death of various types of breast cancer. DCQ causes a signicant accumulation of ROS in cells, which leads to their death.…”

Design, synthesis and biological evaluation of tetrahydroquinoxaline sulfonamide derivatives as colchicine binding site inhibitors

“…3). [33][34][35] In medicinal chemistry, bioisosterism is used as a common strategy for drug design, and sulfonamide moiety is an effective bioisostere for amide group. Therefore, based on our previous work, we replaced the amide with the sulfonamide to design novel colchicine binding site inhibitors and complement the structure-activity relationships (Fig.…”

A newly synthesized nitrogen‐rich derivative of bicyclic quinoxaline—Structural and conceptual DFT reactivity study

“…In the past few decades, design and characterisations of heterocyclic organic compounds have received considerable attention because of their pivotal role and wide application in different areas of life science . Particularly, nitrogen‐containing heterocyclic systems are known to exhibit excellent pharmacological activities .…”