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Furan-2-Carboxamide derivative, A Novel Microtubule Stabilizing Agent Induces Mitotic Arrest and Potentiates Apoptosis in Cancer Cells
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2021-01-08 , DOI: 10.1016/j.bioorg.2020.104586
B Shwetha 1 , M Srinivasa Sudhanva 2 , G S Jagadeesha 3 , N R Thimmegowda 3 , Vivek K Hamse 4 , B T Sridhar 5 , K N Thimmaiah 6 , C S Ananda Kumar 7 , Rangappa Shobith 8 , K S Rangappa 9
Affiliation  

The vital role played by microtubules in the cell division process, marks them as a potential druggable target to decimate cancer. A novel furan-2-carboxamide based small molecule, is a selective microtubule stabilizing agent (MSA) with IC50 ranging from 4 µM – 8 µM in different cancer cell lines. Inhibition of tubulin polymerization or stabilization of tubulin polymers abrogates chromosomal segregation during cell division, results in cell cycle arrest and leads to cell death due to the delayed repair mechanism. A novel furan-2-carboxamide based small molecule exhibited potent anti-proliferative and anti-metastatic property In-Vitro against the panel of cancer cells. Annexin V-FITC/PI, double staining reveals potent cytotoxic effect of SH09 against HeLa cells. FACS analysis displays induction of G2/M arrest and accumulation of subG1 population of cells upon treatment with SH09. Molecular docking study unveils SH09 binding affinity to the Taxol binding pocket of tubulin proteins and MM-GBSA also confirms strong binding energies of SH09 with tubulin proteins.



中文翻译:

Furan-2-Carboxamide 衍生物,一种新型微管稳定剂,可诱导癌细胞的有丝分裂停滞并增强细胞凋亡

微管在细胞分裂过程中发挥的重要作用,标志着它们是一种潜在的药物靶点,可以消灭癌症。基于呋喃-2-甲酰胺的新型小分子,是一种选择性微管稳定剂 (MSA),IC 为50在不同的癌细胞系中范围为 4 µM – 8 µM。抑制微管蛋白聚合或稳定微管蛋白聚合物可消除细胞分裂过程中的染色体分离,导致细胞周期停滞并由于修复机制延迟而导致细胞死亡。一种基于呋喃-2-甲酰胺的新型小分子在体外对癌细胞组表现出有效的抗增殖和抗转移特性。Annexin V-FITC/PI,双染色显示 SH09 对 HeLa 细胞的有效细胞毒作用。FACS 分析显示在用 SH09 处理后诱导 G2/M 期阻滞和亚 G1 细胞群的积累。分子对接研究揭示了 SH09 与微管蛋白的紫杉醇结合口袋的结合亲和力,MM-GBSA 也证实了 SH09 与微管蛋白的强结合能。

更新日期:2021-01-10
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