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新型 N-取代苯甲酰胺类化合物的合成及抗迁移活性评价及其在骨肉瘤治疗中的应用。

Synthesis and biological evaluation of novel N-substituted benzamides as anti-migration agents for treatment of osteosarcoma.

机构信息

Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China.

School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang, 325035, China.

出版信息

Eur J Med Chem. 2021 Mar 15;214:113203. doi: 10.1016/j.ejmech.2021.113203. Epub 2021 Jan 24.

Abstract

A novel series of novel N-substituted (indole or indazole) benzamides were synthesized, and their anti-tumor properties were evaluated. The majority of tested compounds possessed moderate cytotoxicity, but inspiringly, we verified that active compound 5d presents an astonishing advantage by inhibiting the adhesion, migration, and invasion of osteosarcoma (OS) cells in vitro. Mechanistically, we confirmed 5d inhibited the migration ability of OS cells via the expression of genes related to adhesion, migration, and invasion. This effects of 5d suggest that it can be used as a potential chemotherapeutic drug to some aggressive and/or metastatic cancers, as well as in combination with other clinical anti-cancer drugs. In turn, this could enhance the therapeutic effect or reduce the risk of cell migration.

摘要

我们合成了一系列新型的 N-取代(吲哚或吲唑)苯甲酰胺,并评估了它们的抗肿瘤特性。大多数测试的化合物具有中等的细胞毒性,但令人鼓舞的是,我们验证了活性化合物 5d 通过抑制骨肉瘤(OS)细胞的黏附、迁移和侵袭在体外具有惊人的优势。从机制上讲,我们证实 5d 通过抑制与黏附、迁移和侵袭相关的基因的表达来抑制 OS 细胞的迁移能力。5d 的这些作用表明,它可被用作某些侵袭性和/或转移性癌症的潜在化疗药物,以及与其他临床抗癌药物联合使用。反过来,这可以增强治疗效果或降低细胞迁移的风险。

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