含有吡唑-吡啶复合物的姜黄素类似物作为新型抗癌剂:合成、细胞毒性、细胞凋亡诱导和分子模型。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-09-14 DOI:10.1002/cmdc.202500577
Nam Q H Doan, Huyen T T Nguyen, Hoang-Thuc Huynh, Tuyen Ngoc Truong
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引用次数: 0

摘要

近年来,姜黄素类似物不仅显示出有效的抗癌活性,而且还解决了姜黄素本身的一些局限性,因此仍然是科学界研究的一个有前途的焦点。在前人研究成果的基础上,采用苯环与吡啶环的生物等构置换策略,对强效姜黄素类似物与1h -吡唑融合进行结构修饰,开发出一系列新的姜黄素类似物,这些类似物含有吡唑-吡啶杂化物(3a-4h),有望成为抗癌药物。其中,姜黄素类似物4c是最有效的化合物,对多种人类癌细胞系,包括HepG2(肝)、MDA-MB-231(乳腺)和A549(肺)表现出最强的细胞毒性,并对HepG2细胞有显著的诱导凋亡作用。此外,化合物4c预计具有良好的物理化学-药代动力学-毒理学特征,并且在α,β-微管蛋白异源二聚体的秋水草碱结合位点具有有效的结合模式。重要的是,与母体化合物相比,化合物4c的生物等构替代在抗癌活性、物理化学-药代动力学-毒理学特性和结合亲和力方面发挥了有益的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Curcumin Analogs Containing Pyrazole-Pyridine Hybrids as Novel Anticancer Agents: Synthesis, Cytotoxicity, Apoptosis Induction, and Molecular Modeling.

In recent years, curcumin analogs have not only demonstrated potent anticancer activities but have also addressed several limitations of curcumin itself, thereby remaining a promising focus of research within the scientific community. Building upon the findings of our previous studies, structural modifications of potent curcumin analogs fused with 1H-pyrazole are performed by applying the bioisosteric replacement strategy of a benzene ring with a pyridine ring, to develop a series of novel curcumin analogs containing pyrazole-pyridine hybrids (3a-4h) as promising anticancer agents. Among them, curcumin analog 4c emerges as the most potent compound, exhibiting the strongest cytotoxicity against various human cancer cell lines, including HepG2 (liver), MDA-MB-231 (breast), and A549 (lung), as well as significant apoptosis-inducing effects in HepG2 cells. Furthermore, compound 4c is predicted to possess a favorable physicochemical-pharmacokinetic-toxicological profile, as well as an effective binding mode at the colchicine-binding site of the α,β-tubulin heterodimer. Importantly, the bioisosteric replacement in compound 4c is found to exert beneficial effects on its anticancer activities, physicochemical-pharmacokinetic-toxicological properties, and binding affinity, in comparison with its parent compounds.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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