Design, synthesis and biological evaluation of novel curcumin-fluorouracil hybrids as potential anti-cancer agents

IF 5.3 2区 医学 Q1 PHARMACOLOGY & PHARMACY Biochemical pharmacology Pub Date : 2024-09-24 DOI:10.1016/j.bcp.2024.116559
Xiaotong Wang , Xin Li , Xu Zhang , Xuekun Wang , Jie Yang , Guoyun Liu
{"title":"Design, synthesis and biological evaluation of novel curcumin-fluorouracil hybrids as potential anti-cancer agents","authors":"Xiaotong Wang ,&nbsp;Xin Li ,&nbsp;Xu Zhang ,&nbsp;Xuekun Wang ,&nbsp;Jie Yang ,&nbsp;Guoyun Liu","doi":"10.1016/j.bcp.2024.116559","DOIUrl":null,"url":null,"abstract":"<div><div>The latest global cancer data statistics report shows that cancer poses a serious threat to human life and health; The number of new cancer and death cases worldwide is severe. Molecular hybridization is considered an effective strategy for developing new anti-cancer drugs. Curcumin (Cur) is a natural active compound containing Michael receptors that target thioredoxin reductase (TrxR). Fluorouracil (5-FU) is the first anti-metabolic drug synthesized based on certain assumptions for tumor treatment, acting on thymidylate synthase (TS). This study synthesized a series of novel hybrid derivatives of Cur and 5-FU, and evaluated their anti-tumor cell proliferation effects. Several compounds with good cytotoxic activity against tumor cells were discovered; and they exhibited high selectivity towards A549 cells, compared to normal THLE cells. Among them, the hybrid derivative <strong>F-4</strong> has the best anti-proliferative activity in tumor cells. <strong>F-4</strong> can target TrxR, increase reactive oxygen species levels in tumor cells, and lead to tumor cell apoptosis, which may be related to the Michael receptor structure in the chemical structure of <strong>F-4</strong>; <strong>F-4</strong> can also target TS, leading to cell cycle arrest in G0/G1 phase, which may be related to the 5-FU structure in the chemical structure of <strong>F-4</strong>. Moreover, <strong>F-4</strong> can effectively exert anti-tumor activity in mice, significantly reduce tumor volume and weight, and has low toxic side effects. These results indicate that Cur-5-FU hybrid derivative <strong>F-4</strong> is a novel lead compound with <em>in vivo</em> anti-tumor activity and minimal side effects, which deserves further investigation.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0006295224005598","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

The latest global cancer data statistics report shows that cancer poses a serious threat to human life and health; The number of new cancer and death cases worldwide is severe. Molecular hybridization is considered an effective strategy for developing new anti-cancer drugs. Curcumin (Cur) is a natural active compound containing Michael receptors that target thioredoxin reductase (TrxR). Fluorouracil (5-FU) is the first anti-metabolic drug synthesized based on certain assumptions for tumor treatment, acting on thymidylate synthase (TS). This study synthesized a series of novel hybrid derivatives of Cur and 5-FU, and evaluated their anti-tumor cell proliferation effects. Several compounds with good cytotoxic activity against tumor cells were discovered; and they exhibited high selectivity towards A549 cells, compared to normal THLE cells. Among them, the hybrid derivative F-4 has the best anti-proliferative activity in tumor cells. F-4 can target TrxR, increase reactive oxygen species levels in tumor cells, and lead to tumor cell apoptosis, which may be related to the Michael receptor structure in the chemical structure of F-4; F-4 can also target TS, leading to cell cycle arrest in G0/G1 phase, which may be related to the 5-FU structure in the chemical structure of F-4. Moreover, F-4 can effectively exert anti-tumor activity in mice, significantly reduce tumor volume and weight, and has low toxic side effects. These results indicate that Cur-5-FU hybrid derivative F-4 is a novel lead compound with in vivo anti-tumor activity and minimal side effects, which deserves further investigation.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
作为潜在抗癌剂的新型姜黄素-氟尿嘧啶混合物的设计、合成和生物学评价。
最新的全球癌症数据统计报告显示,癌症严重威胁着人类的生命和健康;全球新增癌症病例和死亡病例数量严重。分子杂交被认为是开发新型抗癌药物的有效策略。姜黄素(Cur)是一种天然活性化合物,含有针对硫代氧化还原酶(TrxR)的迈克尔受体。氟尿嘧啶(5-FU)是第一种基于特定假设合成的抗代谢药物,用于治疗肿瘤,作用于胸苷酸合成酶(TS)。本研究合成了一系列 Cur 和 5-FU 的新型混合衍生物,并评估了它们的抗肿瘤细胞增殖效果。研究发现了几种对肿瘤细胞具有良好细胞毒活性的化合物;与正常的THLE细胞相比,它们对A549细胞具有较高的选择性。其中,混合衍生物 F-4 对肿瘤细胞的抗增殖活性最佳。F-4能靶向TrxR,增加肿瘤细胞内活性氧水平,导致肿瘤细胞凋亡,这可能与F-4化学结构中的迈克尔受体结构有关;F-4还能靶向TS,导致细胞周期停滞在G0/G1期,这可能与F-4化学结构中的5-FU结构有关。此外,F-4 还能有效发挥小鼠的抗肿瘤活性,显著减少肿瘤体积和重量,且毒副作用小。这些结果表明,Cur-5-FU 杂交衍生物 F-4 是一种新型先导化合物,具有体内抗肿瘤活性,且副作用小,值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Biochemical pharmacology
Biochemical pharmacology 医学-药学
CiteScore
10.30
自引率
1.70%
发文量
420
审稿时长
17 days
期刊介绍: Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics. The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process. All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review. While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
期刊最新文献
Therapeutic potential of Parkin and its regulation in Parkinson's disease. Interleukin-6 in non-infectious uveitis: Biology, experimental evidence and treatment strategies Acetyl tributyl citrate attenuates 5-fluorouracil-induced inflammation, oxidative stress, and apoptosis in human keratinocytes Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization Targeting fibroblast activation protein with chimeric antigen receptor macrophages.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1