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杂合核碱基-杂环-2-吲哚酮支架作为具有潜在抗癌活性的创新细胞周期调节剂。

Hybrid nucleobase-heterocycle-2-oxindole scaffolds as innovative cell cycle modulators with potential anticancer activity.

作者信息

Abdel-Hafez Gehan Ahmed, Kłopotowska Dagmara, Filip-Psurska Beata, Aboraia Ahmed S, Wietrzyk Joanna, Aboul-Fadl Tarek, Youssef Adel F

机构信息

Medicinal Chemistry Department, Faculty of Pharmacy, Merit University Sohag Egypt.

Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences Wrocław 53-114 Poland.

出版信息

RSC Adv. 2025 Aug 22;15(36):29753-29776. doi: 10.1039/d5ra04997k. eCollection 2025 Aug 18.

DOI:10.1039/d5ra04997k
PMID:40860074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12377214/
Abstract

A series of hybrid molecules 6a-6d-13a-13d combining pyrazolo[3,4-]pyrimidine or aminopurine frameworks with an oxindole moiety were designed as multitarget anticancer agents. Several compounds, especially 8b and 12a-12d, showed potent antiproliferative effects against three human cancer cell lines: A498 (kidney carcinoma), HepG-2 (hepatocellular carcinoma), and MDA-MB-231 (breast adenocarcinoma). Compounds 6b, 7b, 8b, and 12a-12c exhibited remarkable CDK6 inhibition (pIC of up to 7.17), outperforming palbociclib, and VEGFR-2 inhibition comparable to sorafenib. These compounds also inhibited xanthine oxidase. Notably, 12a and 12c induced sub-G1 cell cycle arrest in HepG2 cells. Molecular modeling confirmed stable binding to CDK6 and VEGFR-2, while ADMET profiling suggested favorable pharmacokinetics. These results support 8b and 12a-12c as strong leads for further multitarget cancer therapy development.

摘要

设计了一系列将吡唑并[3,4 -]嘧啶或氨基嘌呤骨架与羟吲哚部分结合的杂化分子6a - 6d - 13a - 13d作为多靶点抗癌剂。几种化合物，特别是8b和12a - 12d，对三种人类癌细胞系：A498（肾癌细胞）、HepG - 2（肝癌细胞）和MDA - MB - 231（乳腺腺癌细胞）显示出强大的抗增殖作用。化合物6b、7b、8b和12a - 12c表现出显著的CDK6抑制作用（pIC高达7.17），优于帕博西尼，并且对VEGFR - 2的抑制作用与索拉非尼相当。这些化合物还抑制黄嘌呤氧化酶。值得注意的是，12a和12c在HepG2细胞中诱导亚G1期细胞周期停滞。分子建模证实了与CDK6和VEGFR - 2的稳定结合，而ADMET分析表明其具有良好的药代动力学。这些结果支持8b和12a - 12c作为进一步开发多靶点癌症治疗的有力先导化合物。

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2
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3
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Sci Rep. 2024 Feb 10;14(1):3419. doi: 10.1038/s41598-024-54021-z.
4
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J Biomol Struct Dyn. 2025 Mar;43(5):2223-2242. doi: 10.1080/07391102.2023.2294175. Epub 2023 Dec 19.
5
Exploring cyclin-dependent kinase inhibitors: a comprehensive study in search of CDK-6 inhibitors using a pharmacophore modelling and dynamics approach.探索细胞周期蛋白依赖性激酶抑制剂：使用药效团建模和动力学方法寻找CDK-6抑制剂的综合研究。
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