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基于石胆酸的咪唑鎓盐在体外和体内抗结直肠癌功效的确立。

Establishment of In Vitro and In Vivo Anticolorectal Cancer Efficacy of Lithocholic Acid-Based Imidazolium Salts.

机构信息

Department of Experimental Pharmacology, Medical University of Bialystok, Szpitalna Street 37, 15-295 Bialystok, Poland.

Department of Organic Chemistry, Medical University of Bialystok, Mickiewicza Street 2A, 15-222 Bialystok, Poland.

出版信息

Int J Mol Sci. 2022 Jun 24;23(13):7019. doi: 10.3390/ijms23137019.

Abstract

Imidazolium salts (IMSs) are the subject of many studies showing their anticancer activities. In this research, a series of novel imidazolium salts substituted with lithocholic acid (LCA) and alkyl chains of various lengths (-) were evaluated against colon cancer cells. A significant reduction in the viability and metabolic activity was obtained in vitro for DLD-1 and HT-29 cell lines when treated with tested salts. The results showed that the activities of tested agents are directly related to the alkyl chain length, where - compounds were the most cytotoxic against the DLD-1 line and - against HT-29. The research performed on the xenograft model of mice demonstrated a lower tendency of tumor growth in the group receiving compound , compared with the group receiving 5-fluorouracil (5-FU). Obtained results indicate the activity of in the induction of apoptosis and necrosis in induced colorectal cancer. LCA-based imidazolium salts may be candidates for chemotherapeutic agents against colorectal cancer.

摘要

咪唑盐(IMSs)是许多研究的主题,这些研究表明它们具有抗癌活性。在这项研究中,一系列新型的咪唑盐用石胆酸(LCA)和不同长度的烷基链取代(-)进行了评估,以对抗结肠癌细胞。当用测试盐处理时,DLD-1 和 HT-29 细胞系的体外活力和代谢活性显著降低。结果表明,测试剂的活性与烷基链长度直接相关,其中-化合物对 DLD-1 系的细胞毒性最大,-对 HT-29 系的细胞毒性最大。在小鼠异种移植模型上进行的研究表明,与接受 5-氟尿嘧啶(5-FU)的组相比,接受化合物-的组的肿瘤生长趋势较低。获得的结果表明,在诱导结直肠癌中,化合物-诱导细胞凋亡和坏死的活性。基于 LCA 的咪唑盐可能是针对结直肠癌的化疗药物的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5db8/9266680/787f991e324a/ijms-23-07019-g001.jpg

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