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研究具有抗白血病活性以及抗结直肠癌和抗乳腺癌作用的 1,4-醌衍生物。

Studies on 1,4-Quinone Derivatives Exhibiting Anti-Leukemic Activity along with Anti-Colorectal and Anti-Breast Cancer Effects.

机构信息

Department of Drug Discovery, Science Farm Ltd., Kumamoto 862-0976, Japan.

Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan.

出版信息

Molecules. 2022 Dec 22;28(1):77. doi: 10.3390/molecules28010077.

DOI:10.3390/molecules28010077
PMID:36615273
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9822417/
Abstract

Colorectal cancer (CRC), breast cancer, and chronic myeloid leukemia (CML) are life-threatening malignancies worldwide. Although potent therapeutic and screening strategies have been developed so far, these cancer types are still major public health problems. Therefore, the exploration of more potent and selective new agents is urgently required for the treatment of these cancers. Quinones represent one of the most important structures in anticancer drug discovery. We have previously identified a series of quinone-based compounds () as anti-CML agents. In the current work, was taken to the National Cancer Institute (NCI) for screening to determine its in vitro antiproliferative effects against a large panel of human tumor cell lines at five doses. revealed significant growth inhibition against HCT-116 CRC and MCF-7 breast cancer cells with 2.00 µM and 2.35 µM GI values, respectively. The MTT test also showed that possessed anticancer effects towards HCT-116 and MCF-7 cells with IC values of 5.22 ± 2.41 μM and 7.46 ± 2.76 μM, respectively. Further experiments indicated that induced apoptosis in both cell lines, and molecular docking studies explicitly suggested that exhibited DNA binding in a similar fashion to previously reported compounds. Based on in silico pharmacokinetic prediction, might display drug-like features enabling this compound to become a lead molecule for future studies.

摘要

结直肠癌(CRC)、乳腺癌和慢性髓性白血病(CML)是全球范围内危及生命的恶性肿瘤。尽管迄今为止已经开发出了有效的治疗和筛查策略,但这些癌症类型仍然是主要的公共卫生问题。因此,迫切需要探索更有效和更具选择性的新药物来治疗这些癌症。醌类化合物是抗癌药物发现中最重要的结构之一。我们之前已经确定了一系列基于醌的化合物()作为抗 CML 药物。在当前的工作中,将化合物带到美国国立癌症研究所(NCI)进行筛选,以确定其在五个剂量下对人肿瘤细胞系的体外增殖抑制作用。结果表明,化合物对 HCT-116 CRC 和 MCF-7 乳腺癌细胞具有显著的生长抑制作用,GI 值分别为 2.00 µM 和 2.35 µM。MTT 试验还表明,化合物对 HCT-116 和 MCF-7 细胞具有抗癌作用,IC 值分别为 5.22 ± 2.41 μM 和 7.46 ± 2.76 μM。进一步的实验表明,化合物在这两种细胞系中均诱导细胞凋亡,分子对接研究明确表明,化合物以与先前报道的化合物类似的方式与 DNA 结合。基于计算机预测的药代动力学,化合物可能具有类药性特征,使该化合物成为未来研究的先导分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/9a86cb492018/molecules-28-00077-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/5a128d1e4be0/molecules-28-00077-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/574bf548e6bb/molecules-28-00077-g006a.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/7077b4949c62/molecules-28-00077-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/66d712a4df65/molecules-28-00077-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/6f68f5bc016c/molecules-28-00077-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/9a86cb492018/molecules-28-00077-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/8f4ff1afc513/molecules-28-00077-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/5261c4f155ef/molecules-28-00077-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/bd93aee47ce6/molecules-28-00077-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/c4a21e16e9ca/molecules-28-00077-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/5a128d1e4be0/molecules-28-00077-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/574bf548e6bb/molecules-28-00077-g006a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/0c2c6d7135ad/molecules-28-00077-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/7077b4949c62/molecules-28-00077-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/66d712a4df65/molecules-28-00077-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/6f68f5bc016c/molecules-28-00077-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb52/9822417/9a86cb492018/molecules-28-00077-g011.jpg

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