发现吡啶-磺胺类杂合体作为一种新的支架，用于开发潜在的 VEGFR-2 抑制剂和凋亡诱导剂。
Discovery of pyridine- sulfonamide hybrids as a new scaffold for the development of potential VEGFR-2 inhibitors and apoptosis inducers.
机构信息
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt.
Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
出版信息
Bioorg Chem. 2021 Jun;111:104842. doi: 10.1016/j.bioorg.2021.104842. Epub 2021 Mar 22.
New sulfonamide derivatives have been synthesized and tested as antitumor agents. All newly synthesized compounds were tested in vitro against 60 lines of human cancer cells. Compound VIIb shows broad-spectrum activity with a mean inhibition value of 91.67% against all cell lines. It exhibited potent anticancer activity with GI50 values of 1.06-8.92 μM relative to most of the tested cancer cell lines. Compound VIIb has been tested for enzyme inhibition activity toward vascular endothelial growth factor receptor 2, where VEGFR-2 was potently inhibited at a lower IC50 value of 3.6 μM, compared with sorafenib (IC50 = 4.8 μM). Hybrid VIIb was also able to induce cell cycle disturbance and apoptosis in Renal UO-31 cells, as shown by DNA flow cytometry and Annexin V-FITC/PI assays. It has also revealed lower Bcl-2 protein expression anti-apoptotic levels and higher BAX, p53, and caspases 3 expression levels.
已合成新的磺胺衍生物并将其用作抗肿瘤剂进行测试。所有新合成的化合物均在体外针对 60 个人类癌细胞系进行了测试。化合物 VIIb 对所有细胞系的平均抑制值为 91.67%，显示出广谱活性。与大多数测试的癌细胞系相比，它具有 GI50 值为 1.06-8.92 μM 的强大抗癌活性。已针对血管内皮生长因子受体 2 对化合物 VIIb 的酶抑制活性进行了测试，其中 VEGFR-2 的抑制作用更强，IC50 值为 3.6 μM，而索拉非尼（IC50 = 4.8 μM）。杂种 VIIb 还能够诱导 Renal UO-31 细胞的细胞周期紊乱和细胞凋亡，如 DNA 流式细胞术和 Annexin V-FITC/PI 测定所示。它还显示出较低的 Bcl-2 蛋白表达水平和抗凋亡水平，以及较高的 BAX、p53 和 caspase 3 表达水平。
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