AI Article Synopsis
- A new series of stilbene-based compounds were developed as dual inhibitors targeting tubulin and HDAC, with one compound, II-19k, showing strong anti-cancer properties in various cell lines.
- II-19k demonstrated a very low IC value, indicating potent activity against hematological and solid tumors, and worked by disrupting microtubules, inhibiting HDACs, and inducing cell death while blocking cell cycle progression.
- In animal tests, II-19k significantly reduced tumor size and weight by over 73% with minimal toxicity, highlighting its potential as an effective antitumor treatment for further research.
Article Abstract
A series of novel stilbene-based derivatives were designed and synthesized as tubulin/HDAC dual-target inhibitors. Among forty-three target compounds, compound II-19k not only exhibited considerable antiproliferative activity in the hematological cell line K562 with IC value of 0.003 μM, but also effectively inhibited the growth of various solid tumor cell lines with IC values ranging from 0.005 to 0.036 μM. 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.
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| http://dx.doi.org/10.1016/j.ejmech.2023.115529 | DOI Listing |
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Article Synopsis
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