meta-Ureidophenoxy-1,2,3-triazole hybrid as a novel scaffold for promising HepG2 hepatocellular carcinoma inhibitors: Synthesis, biological evaluation and molecular docking studies

索拉非尼 化学 MTT法 对接(动物) 肝细胞癌 细胞毒性 立体化学 组合化学 细胞生长 癌症研究 体外 生物化学 生物 医学 护理部
作者
Panupun Limpachayaporn,Sopon Nuchpun,Jitnapa Sirirak,Purin Charoensuksai,Pawaris Wongprayoon,Natthaya Chuaypen,Pisit Tangkijvanich,Apichart Suksamrarn
出处
期刊:Bioorganic & Medicinal Chemistry [Elsevier BV]
卷期号:74: 117048-117048 被引量:2
标识
DOI:10.1016/j.bmc.2022.117048
摘要

Thirty-one meta-ureidophenoxymethyl-1,2,3-triazole derivatives were designed and synthesized via nucleophilic addition, nucleophilic substitution and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The evaluation of their cytotoxicity using MTT assay indicated that almost all derivatives exhibited significantly superior inhibitory activity against hepatocellular carcinoma cell line HepG2 compared to the parental molecule sorafenib (1). Among the series, 5r was the most potent anti-HepG2 agent with IC50 = 1.04 µM, which was almost 5-fold more active than sorafenib (IC50 = 5.06 µM), while the cytotoxic activity against human embryonal lung fibroblast cell line MRC-5 remained comparable to sorafenib. The synthetic derivative 5r, thus, possessed 5.2-time higher selectivity index (SI) than that of sorafenib. Molecular docking studies revealed an efficient interaction of 5r at the same sorafenib's binding region in both B-Raf and VEGFR-2 with lower binding energies than those of sorafenib, consistent with its cytotoxic effect. Furthermore, 5r was proven to induce apoptosis in a dose-dependent manner similar to sorafenib. In addition, the prediction using SwissADME suggested that 5r possessed appropriate drug properties conforming to Veber's studies. These findings revealed that the newly designed meta-ureidophenoxy-1,2,3-triazole hybrid scaffold was a promising structural feature for an efficient inhibition of HepG2. Moreover, derivative 5r emerged as a promising candidate for further development as a targeted anti-cancer agent for hepatocellular carcinoma (HCC).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
ZLX完成签到,获得积分20
1秒前
莫等闲191发布了新的文献求助10
2秒前
哈哈哈发布了新的文献求助10
2秒前
义气沉鱼关注了科研通微信公众号
2秒前
不知道完成签到,获得积分10
4秒前
FashionBoy应助科研通管家采纳,获得10
6秒前
搞怪莫茗应助科研通管家采纳,获得10
6秒前
传奇3应助科研通管家采纳,获得10
6秒前
于浩完成签到 ,获得积分10
6秒前
华仔应助科研通管家采纳,获得10
6秒前
SYLH应助科研通管家采纳,获得10
6秒前
英姑应助科研通管家采纳,获得10
6秒前
领导范儿应助科研通管家采纳,获得10
6秒前
SYLH应助科研通管家采纳,获得10
6秒前
科研通AI2S应助科研通管家采纳,获得10
7秒前
扎心应助科研通管家采纳,获得10
7秒前
SYLH应助科研通管家采纳,获得10
7秒前
Ava应助科研通管家采纳,获得10
7秒前
7秒前
小马甲应助科研通管家采纳,获得10
7秒前
7秒前
我是老大应助科研通管家采纳,获得10
7秒前
8秒前
10秒前
11秒前
11秒前
hhh发布了新的文献求助10
12秒前
13秒前
凩飒给凩飒的求助进行了留言
14秒前
一程发布了新的文献求助10
14秒前
巴黎的防发布了新的文献求助10
15秒前
义气沉鱼发布了新的文献求助10
17秒前
Komorebi完成签到 ,获得积分10
18秒前
18秒前
搜集达人应助小红的忧伤采纳,获得10
19秒前
daying完成签到,获得积分10
21秒前
半糖糖完成签到,获得积分10
21秒前
22秒前
竹简发布了新的文献求助10
22秒前
23秒前
高分求助中
Ophthalmic Equipment Market by Devices(surgical: vitreorentinal,IOLs,OVDs,contact lens,RGP lens,backflush,diagnostic&monitoring:OCT,actorefractor,keratometer,tonometer,ophthalmoscpe,OVD), End User,Buying Criteria-Global Forecast to2029 2000
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 588
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3962475
求助须知:如何正确求助?哪些是违规求助? 3508497
关于积分的说明 11141410
捐赠科研通 3241254
什么是DOI,文献DOI怎么找? 1791445
邀请新用户注册赠送积分活动 872863
科研通“疑难数据库(出版商)”最低求助积分说明 803417