Synthesis and bioevaluation of novel stilbene-based derivatives as tubulin/ HDAC dual-target inhibitors with potent antitumor activities in vitro and in vivo

A series of novel stilbene-based derivatives were designed and synthesized as tubulin/HDAC dual-target in-hibitors. Among forty-three target compounds, compound II-19k not only exhibited considerable anti -proliferative activity in the hematological cell line K562 with IC50 value of 0.003 & mu;M, but also effectively inhibited the growth of various solid tumor cell lines with IC50 values ranging from 0.005 to 0.036 & mu;M. The mechanism studies demonstrated that II-19k could inhibit microtubules and HDACs at the cellular level, block cell cycle arrest at G2 phase, induce cell apoptosis, and reduce solid tumor cells metastasis. What's more, the vascular disrupting effects of compound II-19k were more pronounced than the combined administration of parent compound 8 and HDAC inhibitor SAHA. The in vivo antitumor assay of II-19k also showed the superiority of dual-target inhibition of tubulin and HDAC. II-19k significantly suppressed the tumor volume and effectively reduced tumor weight by 73.12% without apparent toxicity. Overall, the promising bioactivities of II-19k make it valuable for further development as an antitumor agent.

Automated summary

A series of novel stilbene-based derivatives were synthesized and evaluated for their dual-target inhibition of tubulin and HDAC enzymes. Compound II-19k showed significant anti-proliferative activity in K562 hematological cell line and inhibited the growth of various solid tumor cell lines. Mechanism studies revealed its ability to inhibit microtubules and HDACs, induce cell cycle arrest and apoptosis, and reduce tumor cell metastasis. In vivo antitumor assay demonstrated its superiority as a dual-target inhibitor, suppressing tumor volume and weight without apparent toxicity. Overall, the bioactivities of II-19k make it a valuable candidate for further development as an antitumor agent.