Kaito Ohta, Hiromi Ii, Mei Takahashi, Chiami Moyama, Shota Ando, Masaya Mori, Maho Masuda, Hisanori Nambu, Susumu Nakata, Naoto Kojima
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引用次数: 0
摘要
目的:某些癌细胞的存活依赖于氧化磷酸化;因此,抑制这一过程可能是一种很有前景的治疗策略。本研究探讨了线粒体抑制剂 N-乙二醇-含烷基噻吩-3-甲酰胺 3 的结构-活性关系:我们合成并评估了13种具有不同乙二醇单元、杂环和连接基团的类似物(5a-m)对A549非小细胞肺癌细胞的生长抑制作用。我们发现,增加乙二醇单元的数量可显著增强抑制活性。一些类似物激活了单磷酸腺苷激活的蛋白激酶,与 3 类似。值得注意的是,含有四甘醇单位的类似物 5e 能显著抑制体内肿瘤的生长:结论:类似物 5 可能是治疗非小细胞肺癌的潜在药物。
Structure-activity relationships study of N-ethylene glycol-comprising alkyl heterocyclic carboxamides against A549 lung cancer cells.
Aim: Certain cancer cells depend on oxidative phosphorylation for survival; thus, inhibiting this process may be a promising treatment strategy. This study explored the structure-activity relationships of the mitochondrial inhibitor N-ethylene glycol-comprising alkyl thiophene-3-carboxamide 3.Methods & results: We synthesized and evaluated 13 analogs (5a-m) with different ethylene glycol units, heterocycles and connecting groups for their growth-inhibitory effects on A549 non-small cell lung cancer cells. We found that increasing the number of ethylene glycol units significantly enhanced inhibitory activity. Some analogs activated adenosine monophosphate-activated protein kinase, similar to 3. Notably, analog 5e, which contains tetraethylene glycol units, significantly inhibited tumor growth in vivo.Conclusion: Analog 5 may be a potential therapeutic agent for non-small cell lung cancer treatment.
期刊介绍:
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.