Synthesis and evaluation of anticancer and anti-invasive properties of 3-aminowithaferin A and its imine congeners.

IF 3.4 4区医学 Q3 CHEMISTRY, MEDICINAL

Future medicinal chemistry Pub Date : 2025-10-10 DOI:10.1080/17568919.2025.2570971

Shabir Ahmad Mir, Tanzeeba Amin, Gulzar Hussain, Khalid Bashir Mir, Gursimar Kaur, Sameera Firdous, Anindya Goswami, Syed Khalid Yousuf

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引用次数: 0

Abstract

Aim: Synthesisof 3-aminowithaferin A and its imine congeners to identify promising lead molecules for future development as anti-cancer agents.

Materials and methods: 3-Aminowithaferin A was synthesized through aza-Michael addition using liquid ammonia as a nucleophile. In order to obtain imine congeners various aldehydes were allowed to undergo addition-elimination with 3-aminowithaferin A. All the newly synthesized compounds were screened for their cytotoxicity against eight cancers and one normal cell line using MTT assay.

Results and conclusion: One of the imine analogs, referred to as compound 13, exhibited significant antiproliferative and anti-metastatic properties across various cell lines, particularly in triple-negative breast cancer lines, with an IC50 value ranging from 507 nM to 2.475 µM. Compound 13 effectively inhibited the formation of invadopodia and filopodia, underscoring its anti-invasive properties. Additionally, immunoblotting studies demonstrated a consistent decrease in the expression of various epithelial-to-mesenchymal transition (EMT) markers in the presence of compound 13, further confirming its anti-metastatic properties.

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3-氨基糖苷A及其亚胺类同系物的合成及抗癌抗侵性评价。

目的：合成3-氨基内铁素A及其亚胺同系物，寻找有潜力开发抗癌药物的先导分子。材料与方法：以液氨为亲核试剂，采用aza-Michael加成法合成了3-Aminowithaferin A。为了获得亚胺同源物，我们将各种醛类化合物与3-氨基甲苷a进行加消处理，用MTT法对新合成的化合物进行了对8种癌症和1种正常细胞的细胞毒性筛选。结果和结论：其中一种亚胺类似物，称为化合物13，在各种细胞系中表现出显著的抗增殖和抗转移特性，特别是在三阴性乳腺癌细胞系中，其IC50值为507 nM至2.475µM。化合物13能有效抑制侵入足和丝状足的形成，显示其抗侵入性。此外，免疫印迹研究表明，化合物13存在时，各种上皮-间质转化（EMT）标志物的表达持续下降，进一步证实了其抗转移特性。

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来源期刊

Future medicinal chemistry CHEMISTRY, MEDICINAL-

CiteScore

5.80

自引率

2.40%

发文量

118

审稿时长

4-8 weeks

期刊介绍： Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.