Zutião Arthur Deponte, Pachane Bianca Cruz, Nunes Paulo Sérgio Gonçalves, Vidal Herika Danielle Almeida, Selistre-de-Araujo Heloisa Sobreiro, Corrêa Arlene Gonçalves, Cominetti Marcia Regina, Fuzer Angelina Maria
Department of Gerontology, Universidade Federal de São Carlos - UFSCar, São Carlos, São Paulo 13565-905, Brazil.
Biochemistry and Molecular Biology Laboratory, Department of Physiological Sciences, Universidade Federal de São Carlos - UFSCar, São Carlos, São Paulo 13565-905, Brazil.
ACS Med Chem Lett. 2025 Feb 10;16(3):436-443. doi: 10.1021/acsmedchemlett.4c00596. eCollection 2025 Mar 13.
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 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.
乳腺癌是全球主要死因之一，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，缺乏靶向治疗方法，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诊疗试剂是个性化癌症管理的有前景的策略。将具有生物学相关性的部分与不同作用模式相结合的杂化化合物可以增强细胞毒性并改善药理学性质。我们专注于一种含有香豆素、三唑和[10]-姜酚的杂化物，[10]-姜酚是一种在三阴性乳腺癌中具有已知抗转移潜力的化合物。与单独的香豆素和[10]-姜酚对照相比，LSPN281杂化物在三阴性乳腺癌细胞系中表现出优异的细胞毒性活性。此外，该杂化物显示出增强的细胞摄取和线粒体定位，表明其作为三阴性乳腺癌诊疗试剂的潜力。
