Structurally simplified biphenyl combretastatin A4 derivatives retain in vitro anti-cancer activity dependent on mitotic arrest

摘要: The cis-stilbene, combretastatin A4 (CA4), is a potent microtubule targeting and vascular damaging agent. Despite promising results at the pre-clinical level extensive clinical evaluation, CA4 has yet to be approved for therapeutic use. One impediment development of an inherent conformational instability about ethylene linker, which joins two aromatic rings. We have previously published preliminary data regarding structurally simplified biphenyl derivatives CA4, lacking retain anti-proliferative pro-apoptotic activity, albeit higher doses. Our current study provides more comprehensive evaluation properties in both 2D 3D cancerous non-cancerous cell models. Computational analysis revealed that cytotoxicity analogues correlates with predicted tubulin affinity. Additional mechanistic found their anti-cancer activity dependent on prolonged mitotic arrest, similar manner CA4. Lastly, we shown cancer cells deficient extrinsic pathway apoptosis experience delayed death following treatment or analogues. Biphenyl represent mechanism action. warrant vivo examination evaluate potential as agents.