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具有抗癌活性和选择性的水杨醛苯甲酰腙:设计、合成及体外评价

Salicylaldehyde Benzoylhydrazones with Anticancer Activity and Selectivity: Design, Synthesis, and In Vitro Evaluation.

作者信息

Nikolova-Mladenova Boryana, Mihaylova Rositsa, Atanasova Mariyana, Zhivkova Zvetanka, Doytchinova Irini

机构信息

Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.

Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University of Sofia, 2 Dunav Str., 1000 Sofia, Bulgaria.

出版信息

Molecules. 2025 Feb 22;30(5):1015. doi: 10.3390/molecules30051015.

Abstract

Dimethoxy derivatives of salicylaldehyde benzoylhydrazone containing a methoxy group on both aromatic rings were designed and synthesized. The compounds were obtained in high yields, and their structures were confirmed by elemental analysis and various spectral techniques. In vitro evaluation of dimethoxy hydrazones demonstrated potent activity against the leukemic cell lines at low micro- and nanomolar concentrations. Remarkably, two dimethoxy analogs showed exceptional antileukemic selectivity, with no toxicity observed in normal human embryonic kidney HEK-293 cells. In silico modeling identified likely interactions with the target, human cAbl kinase, and suggested a possible mechanism for their antileukemic activity.

摘要

设计并合成了在两个芳香环上均含有甲氧基的水杨醛苯甲酰腙二甲氧基衍生物。这些化合物的产率很高,其结构通过元素分析和各种光谱技术得以确认。对二甲氧基腙的体外评估表明,它们在低微摩尔和纳摩尔浓度下对白血病细胞系具有强大的活性。值得注意的是,两种二甲氧基类似物表现出卓越的抗白血病选择性,在正常人胚肾HEK-293细胞中未观察到毒性。计算机模拟确定了与靶标人cAbl激酶可能的相互作用,并提出了它们抗白血病活性的可能机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/040d/11901818/1e3dbb71207e/molecules-30-01015-sch001.jpg

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