Enhanced Cytotoxicity of [10]-Gingerol-Coumarin-Triazole Hybrid as a Theranostic Agent for Triple Negative Breast Cancer.

IF 3.5 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2025-02-10 eCollection Date: 2025-03-13 DOI:10.1021/acsmedchemlett.4c00596

Arthur Deponte Zutião, Bianca Cruz Pachane, Paulo Sérgio Gonçalves Nunes, Herika Danielle Almeida Vidal, Heloisa Sobreiro Selistre-de-Araujo, Arlene Gonçalves Corrêa, Marcia Regina Cominetti, Angelina Maria Fuzer

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引用次数: 0

Abstract

A leading cause of death worldwide, breast cancer is the second most prevalent cancer in women. Triple-negative breast cancer is an aggressive subtype that lacks targeted therapies and requires novel therapeutic approaches in clinical practice to improve the overall survival. Theranostic agents that integrate diagnostic and therapeutic capabilities in a single entity are promising strategies for personalized cancer management. Hybrid compounds combining biologically relevant moieties with different modes of action can enhance cytotoxicity and improve pharmacological properties. We focus on a hybrid containing coumarin, triazole, and [10]-gingerol, a compound with known antimetastatic potential in TNBC. The LSPN281 hybrid exhibited superior cytotoxic activity in a TNBC cell line in vitro compared to the individual coumarin and [10]-gingerol controls. Additionally, the hybrid shows enhanced cellular uptake and mitochondrial localization, suggesting its potential as a theranostic agent for TNBC.

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[10]-姜辣素-香豆素-三唑复合物治疗三阴性乳腺癌的细胞毒性增强研究

乳腺癌是世界范围内导致死亡的主要原因之一，也是女性中第二常见的癌症。三阴性乳腺癌是一种侵袭性亚型，缺乏靶向治疗，在临床实践中需要新的治疗方法来提高总体生存率。将诊断和治疗能力整合在一个实体中的治疗药物是个性化癌症管理的有前途的策略。结合具有不同作用模式的生物相关部分的杂化化合物可以增强细胞毒性和改善药理特性。我们专注于一种含有香豆素、三唑和[10]-姜辣素的混合物，[10]-姜辣素是一种已知在TNBC中具有抗转移潜力的化合物。与单独的香豆素和[10]-姜辣素对照相比，LSPN281杂种在体外TNBC细胞系中表现出优越的细胞毒活性。此外，该杂交体显示出增强的细胞摄取和线粒体定位，表明其作为TNBC治疗药物的潜力。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.