Synthesis, characterization and biological evaluation of formononetin derivatives as anticancer agents

IF 3.1 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Research Pub Date : 2025-08-28 DOI:10.1007/s00044-025-03460-y

Neha Bhardwaj, Kajal Kaliya, Sudesh Kumar Yadav, Ankit Saneja

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引用次数: 0

Abstract

Formononetin (FMN), a natural isoflavone with broad biological activity, has emerged as a potential lead molecule as an anticancer agent. In this work, different FMN ester derivatives were synthesized via an acylation reaction (3a-d). The structural characterization and purity of the compounds were confirmed through NMR, HRMS, and HPLC analysis. Among the synthesized derivatives, the 4-Morpholinecarbonyl chloride conjugated FMN (FMN-4Morpho; 3b) demonstrated significantly (p < 0.05) enhanced cytotoxicity against multiple cancer cell lines, including A549, B16F10, and 4T1, while showing no notable toxicity up to 200 μM in non-cancerous L929 fibroblasts and RAW 264.7 macrophages, indicating good biocompatibility. The mechanistic evaluations in A549 and 4T1 cells revealed elevated ROS production, disruption of mitochondrial membrane potential, and increased apoptosis, as revealed by JC-1 and Annexin V-FITC/PI staining. Additionally, FMN-4Morpho suppressed colony formation and cell migration, downregulated cyclin A, cyclin D1, MMP-2, and MMP-9, and upregulated p53 and Bax expression, thereby lowering the Bcl-2/Bax ratio. The findings highlight FMN-4Morpho as a promising therapeutic candidate with improved anticancer efficacy.

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刺芒柄花素衍生物抗癌作用的合成、表征及生物学评价

刺芒柄花素（FMN）是一种具有广泛生物活性的天然异黄酮，已成为潜在的抗癌先导分子。在这项工作中，通过酰化反应（3a-d）合成了不同的FMN酯衍生物。通过NMR、HRMS、HPLC等方法对化合物进行了结构表征和纯度鉴定。在所合成的衍生物中，4- morpholinecar羰基氯偶联的FMN （FMN- 4morpho; 3b）对多种癌细胞系（包括A549、B16F10和4T1）的细胞毒性显著（p < 0.05）增强，而对非癌性L929成纤维细胞和RAW 264.7巨噬细胞在200 μM范围内无明显毒性，表明具有良好的生物相容性。JC-1和Annexin V-FITC/PI染色显示，A549和4T1细胞的机制评估显示ROS生成升高，线粒体膜电位破坏，凋亡增加。此外，FMN-4Morpho抑制集落形成和细胞迁移，下调cyclin A、cyclin D1、MMP-2和MMP-9，上调p53和Bax表达，从而降低Bcl-2/Bax比值。这些发现突出了FMN-4Morpho作为一种有希望的治疗候选者，具有提高的抗癌功效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Chemistry Research 医学-医药化学

CiteScore

4.70

自引率

3.80%

发文量

162

审稿时长

5.0 months

期刊介绍： Medicinal Chemistry Research (MCRE) publishes papers on a wide range of topics, favoring research with significant, new, and up-to-date information. Although the journal has a demanding peer review process, MCRE still boasts rapid publication, due in part, to the length of the submissions. The journal publishes significant research on various topics, many of which emphasize the structure-activity relationships of molecular biology.