Novel beta-lactam substituted benzenesulfonamides: in vitro enzyme inhibition, cytotoxic activity and in silico interactions

化学 立体化学 碳酸酐酶 部分 活动站点 对接(动物) 体外 顺铂 质子核磁共振 生物信息学 乙酰唑胺 碳-13核磁共振 生物化学 医学 护理部 外科 化疗 麻醉 基因
作者
Özcan Güleç,Cüneyt Türkeş,Mustafa Arslan,Yeliz Demir,Büşra Dinçer,Abdulilah Ece,Şükrü Beydemir
出处
期刊:Journal of Biomolecular Structure & Dynamics [Taylor & Francis]
卷期号:: 1-19 被引量:31
标识
DOI:10.1080/07391102.2023.2240889
摘要

AbstractIn this study, a library of twelve beta-lactam-substituted benzenesulfonamides (5a–l) was synthesized using the tail-approach method. The compounds were characterized using IR, 1H NMR, 13C NMR and elemental analysis techniques. These newly synthesized compounds were tested for their ability to inhibit the activity of two carbonic anhydrases (hCA) isoforms, I and II, and acetylcholinesterase (AChE) in vitro. The results showed that the synthesized compounds were potent inhibitors of hCA I, with KIs in the low nanomolar range (66.60–278.40 nM) than the reference drug acetazolamide (AAZ), which had a KI of 439.17 nM. The hCA II was potently inhibited by compounds 5a, 5d–g and 5l, with KIs of 69.56, 39.64, 79.63, 74.76, 78.93 and 74.94 nM, respectively (AAZ, KI of 98.28 nM). Notably, compound 5a selectively inhibited hCA II with a selectivity of > 4-fold over hCA I. In terms of inhibition of AChE, the synthesized compounds had KIs ranging from 30.95 to 154.50 nM, compared to the reference drug tacrine, which had a KI of 159.61 nM. Compounds 5f, 5h and 5l were also evaluated for their ability to inhibit the MCF-7 cancer cell line proliferation and were found to have promising anticancer activity, more potent than 5-fluorouracil and cisplatin. Molecular docking studies suggested that the sulfonamide moiety of these compounds fits snugly into the active sites of hCAs and interacts with the Zn2+ ion. Furthermore, molecular dynamics simulations were performed for 200 ns to assess the stability and dynamics of each enzyme-ligand complex. The acceptability of the compounds based on Lipinski’s and Jorgensen’s rules was also estimated from the ADME/T results. These results indicate that the synthesized molecules have the potential to be developed into effective and safe inhibitors of hCAs and AChE and could be lead agents.Communicated by Ramaswamy H. SarmaKeywords: Carbonic anhydraseacetylcholinesterasebeta-lactamMCF-7in silico study Disclosure statementNo potential conflict of interest was reported by the authors.Data availability statementData will be made available on request. All spectra that support the characterization of the compounds is provided in the Supporting Information.AcknowledgementsAuthor Özcan Güleç is a 100/2000 The Council of Higher Education (CoHE) Ph.D. Scholar in the Organic Smart and Innovative Materials Subsection.Correction StatementThis article has been corrected with minor changes. These changes do not impact the academic content of the article.Additional informationFundingThis work was supported by the Research Fund of Sakarya University (grant number 2021-7-24-56), the Research Fund of Erzincan Binali Yıldırım University (grant number TSA-2020-729), and the Research Fund of Anadolu University (grant number 2102S003).
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
yundong完成签到,获得积分10
2秒前
科研通AI5应助Karen_Liu采纳,获得10
2秒前
小猪要快乐完成签到,获得积分10
3秒前
晓晓马儿完成签到 ,获得积分10
6秒前
天天摸鱼完成签到,获得积分10
6秒前
6秒前
7秒前
量子星尘发布了新的文献求助10
8秒前
现代雁桃完成签到,获得积分10
8秒前
科研通AI2S应助lvsehx采纳,获得10
8秒前
吕大本事完成签到,获得积分10
9秒前
温柔的语柔完成签到,获得积分10
10秒前
阳光的荠完成签到 ,获得积分10
11秒前
Hancock完成签到 ,获得积分0
11秒前
11秒前
12秒前
13秒前
14秒前
15秒前
W29完成签到,获得积分0
16秒前
大爷发布了新的文献求助10
18秒前
王梅完成签到,获得积分10
19秒前
19秒前
asjm完成签到 ,获得积分10
19秒前
岁月星辰发布了新的文献求助10
20秒前
20秒前
21秒前
77完成签到,获得积分10
21秒前
Selonfer完成签到,获得积分10
22秒前
萂昕完成签到 ,获得积分10
23秒前
NexusExplorer应助wqy采纳,获得10
23秒前
spy完成签到,获得积分10
23秒前
nn完成签到 ,获得积分10
25秒前
25秒前
无情山水发布了新的文献求助10
25秒前
小马甲应助执着的导师采纳,获得10
27秒前
tiantiantian完成签到,获得积分10
27秒前
qweqwe完成签到,获得积分10
28秒前
量子星尘发布了新的文献求助10
29秒前
伪电气白兰完成签到,获得积分10
30秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Zeolites: From Fundamentals to Emerging Applications 1500
Encyclopedia of Materials: Plastics and Polymers 1000
Architectural Corrosion and Critical Infrastructure 1000
Early Devonian echinoderms from Victoria (Rhombifera, Blastoidea and Ophiocistioidea) 1000
Hidden Generalizations Phonological Opacity in Optimality Theory 1000
Handbook of Social and Emotional Learning, Second Edition 900
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 内科学 生物化学 物理 计算机科学 纳米技术 遗传学 基因 复合材料 化学工程 物理化学 病理 催化作用 免疫学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 4919033
求助须知:如何正确求助?哪些是违规求助? 4191171
关于积分的说明 13016365
捐赠科研通 3961419
什么是DOI,文献DOI怎么找? 2171659
邀请新用户注册赠送积分活动 1189623
关于科研通互助平台的介绍 1098231