基于靶点的抗癌甘草酸苷衍生物:设计、合成、生物学评估和分子对接研究

IF 1.3 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Bulletin of the Chemical Society of Ethiopia Pub Date : 2024-07-12 DOI:10.4314/bcse.v38i5.14
Gaber O. Moustafa, A. Kalmouch, Somaia S. Abd El-Karim, Eman S. Nossier, Marwa M. Mounier, Heba El-Sayed, Abdulrahman A. Almehizia, Ahmed M. Naglah, Amer A. Zen
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引用次数: 0

摘要

18-甘草次酸(GA)是从中药甘草根中分离出来的主要活性成分,具有很强的抗癌作用。这项工作的基础是发现和设计全新的 18-甘草次酸(GA)氨基酸肽和肽酯类似物。细胞毒性评估显示,尽管测试的肽 2、3、4、6 和 7 在 MCF-7 和 HCT-116 癌细胞中具有良好的细胞毒性活性,IC50 值分别为 5.1-7.4 和 6.6-72.7 µg/mL。此外,与典型的人真皮成纤维细胞(BJ-1)细胞系相比,所有新生产的对肿瘤细胞系具有中度至高度活性的 GA 肽都具有良好的安全性。有趣的是,2、4 和 6 对 CDK-2、血管内皮生长因子受体-2 和 PDGFR-α 激酶具有出色的多靶点抑制作用。此外,由于肽 6 是最活跃的细胞毒性药物,因此我们选择它作为一个示例候选药物,在体外研究中考察它对许多凋亡标志物的影响,包括 Bax、caspase-3 和 7、DNA 断裂、BCl-2、p53 和微管蛋白聚合抑制。对所有新型类似物都进行了抗菌效果测试,并与一组微生物菌株进行了比较。肽 6 还在先前激酶的活性位点进行了分子对接模拟。关键词:多肽 甘草次酸 抗癌 细胞毒性 分子对接 抗菌活性 Bull.Chem.Soc.2024, 38(5), 1369-1392. DOI: https://dx.doi.org/10.4314/bcse.v38i5.14
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Target-based anticancer glycyrrhetinic derivatives: Design, synthesis, biological assessment and molecular docking studies
18-Glycyrrhetinic acid (GA) is regarded as the principal active component isolated from the Chinese medicinal plant of licorice root, and it has considerable anticancer actions. This work was built on the discovery and design of brand-new 18-glycyrrhetinic acid (GA) amino acid peptides and peptide ester analogs. The cytotoxic evaluation exhibited that despite the promising cytotoxic activity of the tested peptides 2, 3, 4, 6, and 7 in MCF-7 and HCT-116 cancer cells, with IC50 values ranging from 5.1-7.4 and 6.6-72.7 µg/mL, respectively. Furthermore, all freshly produced GA-peptides with moderate to high activity on tumor cell lines produced a favorable safety profile versus typical human dermal fibroblasts (BJ-1) cellular lineage. Interestingly, 2, 4 and 6 demonstrated excellent multitargeting inhibitory profiles against CDK-2, VEGFR-2, and PDGFR-α kinases. Moreover, since peptide 6 was the most active cytotoxic agent, it was chosen as an illustrative candidate to examine its influence on many apoptotic markers in invitro studies, including Bax, caspase-3 and 7, DNA fragmentation, BCl-2, p53, and tubulin polymerization inhibition. All novel analogs were tested for their antimicrobial efficacy versus a panel of microbial strains. The peptide 6 was also subjected to molecular docking simulations in the active sites of the prior kinases. KEY WORDS: Peptides, Glycyrrhetinic acid, Anticancer, Cytotoxicity, Molecular docking, Antimicrobial activity Bull. Chem. Soc. Ethiop. 2024, 38(5), 1369-1392.                                                             DOI: https://dx.doi.org/10.4314/bcse.v38i5.14
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来源期刊
CiteScore
2.20
自引率
8.30%
发文量
113
审稿时长
6-12 weeks
期刊介绍: The Bulletin of the Chemical Society of Ethiopia (BCSE) is a triannual publication of the Chemical Society of Ethiopia. The BCSE is an open access and peer reviewed journal. The BCSE invites contributions in any field of basic and applied chemistry.
期刊最新文献
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