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• W4206586521 endingPage "105625" @default.
• W4206586521 startingPage "105625" @default.
• W4206586521 abstract "Multi-target drugs design has become an active research field because of their advantages in cancer treatment. In present study, HDAC inhibitors pharmacophore and 2-methoxyestradiol(2ME2) were combined into a new hybrid molecule for the first time. Forty-seven 2ME2 derivatives were synthesized and evaluated for antiproliferative activity. In particular, compound 4s exhibited a dual inhibition of tubulin polymerization and HDAC (IC50 = 0.06 µM toward HDAC2) activity, as well as the most potent cytotoxicity IC50 values of 0.37-4.84 µM against six cancer cell lines. Compound 4s remarkably disrupted microtubule networks, arrested cell cycle at G2/M phase, induced mitochondrial membrane potential collapse and eventually apoptosis in A549 cells. Notably, 4s was discovered to potently imped the tube-formation of HUVECs and prohibited the proliferation, migration, and invasion of HUVECs, as well as A549 cells. In addition, the anti-angiogenic and anti-metastasis activities were demonstrated via a zebrafish model test. All these beneficial anticancer activities together with its high selectivity toward noncancer cells, suggested 4s may deserves consideration for cancer therapy." @default.
• W4206586521 created "2022-01-25" @default.
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• W4206586521 date "2022-03-01" @default.
• W4206586521 modified "2023-10-16" @default.
• W4206586521 title "2-Methoxydiol derivatives as new tubulin and HDAC dual-targeting inhibitors, displaying antitumor and antiangiogenic response" @default.
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• W4206586521 doi "https://doi.org/10.1016/j.bioorg.2022.105625" @default.
• W4206586521 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35078046" @default.
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