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呋喃-2-甲酰胺衍生物,一种新型微管稳定剂,可诱导有丝分裂停滞并增强癌细胞中的细胞凋亡。

Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells.

机构信息

Department of Nanotechnology, CPGS, Visvesvaraya Technological University, Muddenahalli, Karnataka 562101, India.

Adichunchanagiri Institute for Molecular Medicine, AIMS, Adichunchanagiri University, BG Nagara 571448, Karnataka 02, India; Faculty of Natural Sciences, Adichunchanagiri University, BG Nagara 571448, Karnataka, India.

出版信息

Bioorg Chem. 2021 Mar;108:104586. doi: 10.1016/j.bioorg.2020.104586. Epub 2021 Jan 8.

Abstract

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 IC ranging from 4 µM to 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.

摘要

微管在细胞分裂过程中起着至关重要的作用,这使得它们成为一种有潜力的药物靶点,可以消灭癌症。一种新型的呋喃-2-甲酰胺小分子,是一种选择性微管稳定剂(MSA),在不同的癌细胞系中的 IC 范围为 4µM 至 8µM。微管聚合的抑制或微管聚合物的稳定会在细胞分裂过程中破坏染色体分离,导致细胞周期停滞,并由于延迟的修复机制导致细胞死亡。一种新型的呋喃-2-甲酰胺小分子在体外对一系列癌细胞表现出强大的抗增殖和抗转移特性。Annexin V-FITC/PI 双染显示 SH09 对 HeLa 细胞具有很强的细胞毒性作用。FACS 分析显示,用 SH09 处理后,G2/M 期阻滞和亚 G1 期细胞群的积累。分子对接研究揭示了 SH09 与微管蛋白 Taxol 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。

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