Discovery of New Non-Symmetrical Heterocyclic Pentanoid Derivatives Targeting Metastatic Triple-Negative Breast Cancer

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-04-08 DOI:10.1016/j.bmcl.2025.130232

Poh Yen Khor , Johnson Stanslas , Nurulfazlina Edayah Rasol , Kok Meng Chan , Phooi Yan Mock , Kok Wai Lam

引用次数: 0

Abstract

This study describes the synthesis and structure-activity relationship (SAR) analysis of non- symmetrical heterocyclic pentanoid derivative as potential anti-cancer agents. The lead compound, 5d, exhibited potent (IC₅₀ = 0.38 ± 0.05 μM) and selective (Selectivity Index: 2–9) growth inhibitory effects on the metastatic triple-negative breast cancer (TNBC) cells. Mechanistic studies revealed that 5d attenuates proteasomal degradation activity via the ubiquitin-proteasome pathway, leading to G2/M phase cell cycle arrest and the induction of apoptotic cell death.

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发现靶向转移性三阴性乳腺癌的新型非对称杂环戊烷类衍生物

本文研究了非对称杂环戊烷衍生物的合成及其构效关系分析。先导化合物5d对转移性三阴性乳腺癌（TNBC）细胞具有强效（IC50 = 0.38±0.05 μM）和选择性（选择性指数：2-9）的生长抑制作用。机制研究表明，5d通过泛素-蛋白酶体途径减弱蛋白酶体降解活性，导致G2/M期细胞周期阻滞，诱导凋亡细胞死亡。

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

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.