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具有抗增殖活性并与阿霉素协同作用于人类结肠癌细胞系的菲单体和二聚体

Phenanthrene Monomers and Dimers from with Antiproliferative Activity and Synergistic Effect with Doxorubicin Against Human Colon Cancer Cell Lines.

作者信息

Barta Anita, Kincses Annamária, Purger Dragica, Spengler Gabriella, Hohmann Judit, Vasas Andrea

机构信息

Institute of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, Hungary.

HUN-REN-USZ Biologically Active Natural Products Research Group, University of Szeged, 6720 Szeged, Hungary.

出版信息

Int J Mol Sci. 2025 Aug 8;26(16):7665. doi: 10.3390/ijms26167665.

Abstract

Continuing our search for bioactive compounds in species from the Juncaceae family, we investigated . The structures of five previously undescribed phenanthrenes-tenuins A-E (-)-and 14 known phenanthrenes (-), along with other components, were isolated and characterized using nuclear magnetic resonance and high-resolution mass spectrometry measurements. The antiproliferative activity of all of the isolated phenanthrenes was evaluated against the human colorectal adenocarcinoma cell lines COLO 205 (doxorubicin-sensitive) and COLO 320 (doxorubicin-resistant), as well as a non-tumorigenic human fibroblast cell line (CCD-19Lu), using the MTT viability assay. Diphenanthrenes , , and showed the most potent antiproliferative effects, with IC values ranging from 7.60 to 17.32 μM; however, these compounds lacked selectivity toward cancer cells. To explore potential chemosensitizing properties, the synergistic effects of the phenanthrenes with the anticancer drug doxorubicin were also examined in the COLO 320 cells. Notably, compound exhibited very strong synergism (CI = 0.021), indicating a highly potent interaction. These findings highlight as a valuable source of phenanthrenes and demonstrate the synergistic anticancer potential of natural phenanthrenes with doxorubicin, offering promising prospects for overcoming multidrug resistance in colorectal cancer therapy.

摘要

在继续寻找灯心草科植物中的生物活性化合物的过程中,我们进行了研究。利用核磁共振和高分辨率质谱测量,分离并鉴定了五种之前未描述过的菲类化合物——灯心草素A - E(-)以及14种已知的菲类化合物(-),还有其他成分。使用MTT活力测定法,评估了所有分离出的菲类化合物对人结肠腺癌细胞系COLO 205(对阿霉素敏感)和COLO 320(对阿霉素耐药)以及非致瘤性人成纤维细胞系(CCD - 19Lu)的抗增殖活性。二菲类化合物、和表现出最有效的抗增殖作用,IC值范围为7.60至17.32 μM;然而,这些化合物对癌细胞缺乏选择性。为了探索潜在的化学增敏特性,还在COLO 320细胞中检测了菲类化合物与抗癌药物阿霉素的协同作用。值得注意的是,化合物表现出非常强的协同作用(CI = 0.021),表明存在高效的相互作用。这些发现突出了作为菲类化合物的宝贵来源,并证明了天然菲类化合物与阿霉素的协同抗癌潜力,为克服结直肠癌治疗中的多药耐药性提供了有前景的展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d2b/12386809/61b405547306/ijms-26-07665-g001.jpg

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