Synthesis, antiproliferative activity and molecular docking studies of neo- and isocryptolepine conjugates

IF 2.2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Journal of the Iranian Chemical Society Pub Date : 2024-09-10 DOI:10.1007/s13738-024-03078-8
Kholoud Heshmat, Asmaa T. Mohamed, Samah A. Loutfy, Ramy Mohamed AbdElaziz, Mehrez E. El-Naggar, Mohamed A. Hamed, Mohamed Atef, Elbadawy A. Kamoun, Ibrahim El-Tantawy El-Sayed, Yasmine S. Moemen
{"title":"Synthesis, antiproliferative activity and molecular docking studies of neo- and isocryptolepine conjugates","authors":"Kholoud Heshmat,&nbsp;Asmaa T. Mohamed,&nbsp;Samah A. Loutfy,&nbsp;Ramy Mohamed AbdElaziz,&nbsp;Mehrez E. El-Naggar,&nbsp;Mohamed A. Hamed,&nbsp;Mohamed Atef,&nbsp;Elbadawy A. Kamoun,&nbsp;Ibrahim El-Tantawy El-Sayed,&nbsp;Yasmine S. Moemen","doi":"10.1007/s13738-024-03078-8","DOIUrl":null,"url":null,"abstract":"<div><p>A series of twelve conjugates <b>9a-c, 10a-c</b>, <b>11a-c,</b> and <b>12a-c</b> based on naturally occurring neo- and isocryptolepines <b>I</b> and <b>II</b> were synthesized and characterized. The synthetic pathways involved nucleophilic substitution reaction of the preprepared amines <b>4a-c</b> and <b>5a-c</b> with 1-(4-bromobutyl)indole derivatives <b>8a</b> and <b>8b</b>, respectively, in aprotic solvent under heating. The structures of the synthesized conjugates were elucidated by <b>FTIR, </b><sup><b>1</b></sup><b>H NMR</b>, <sup><b>13</b></sup><b>C NMR,</b> and <b>MS</b> spectrometry and showed data consistence with the expected structures. The antiproliferative activity of <b>9a-c, 10a-c, 11a-c</b> and <b>12a-c</b> was evaluated against HepG-2 and HCT-116 cancer cell lines using normal cells and reference drug paclitaxel. The screening results revealed that <b>9b</b> and <b>9c</b> were the most active conjugates against HepG-2 and HCT-116 cancer cell lines with IC<sub>50</sub>: 8.49, 9.52, 16.87, 21.75 µM, respectively, using <i>paclitaxel</i> as a reference drug. It is worth noting that <b>9b</b> and <b>9c</b> were more selective toward cancer cells versus normal Vero cells. To rationalize the anticancer activity and selectivity of <b>9b</b> and <b>9c,</b> we have performed molecular docking study against human topoisomerases I and II for better understanding of their anticancer activities in atomic level. Molecular docking studies revealed that the presence of planar indoloquinoline fused four rings and a flexible side chain pharmacophores together improve DNA-intercalation and inhibition of DNA-Topo isomerases activity.</p></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Iranian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13738-024-03078-8","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

A series of twelve conjugates 9a-c, 10a-c, 11a-c, and 12a-c based on naturally occurring neo- and isocryptolepines I and II were synthesized and characterized. The synthetic pathways involved nucleophilic substitution reaction of the preprepared amines 4a-c and 5a-c with 1-(4-bromobutyl)indole derivatives 8a and 8b, respectively, in aprotic solvent under heating. The structures of the synthesized conjugates were elucidated by FTIR, 1H NMR, 13C NMR, and MS spectrometry and showed data consistence with the expected structures. The antiproliferative activity of 9a-c, 10a-c, 11a-c and 12a-c was evaluated against HepG-2 and HCT-116 cancer cell lines using normal cells and reference drug paclitaxel. The screening results revealed that 9b and 9c were the most active conjugates against HepG-2 and HCT-116 cancer cell lines with IC50: 8.49, 9.52, 16.87, 21.75 µM, respectively, using paclitaxel as a reference drug. It is worth noting that 9b and 9c were more selective toward cancer cells versus normal Vero cells. To rationalize the anticancer activity and selectivity of 9b and 9c, we have performed molecular docking study against human topoisomerases I and II for better understanding of their anticancer activities in atomic level. Molecular docking studies revealed that the presence of planar indoloquinoline fused four rings and a flexible side chain pharmacophores together improve DNA-intercalation and inhibition of DNA-Topo isomerases activity.

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
新鸦胆子碱和异鸦胆子碱共轭物的合成、抗增殖活性和分子对接研究
以天然新吲哚和异吲哚啉 I 和 II 为基础,合成了一系列共轭物 9a-c、10a-c、11a-c 和 12a-c,并对其进行了表征。合成过程包括在加热的非烷基溶剂中,将制备的胺 4a-c 和 5a-c 分别与 1-(4-溴丁基)吲哚衍生物 8a 和 8b 进行亲核取代反应。通过傅立叶变换红外光谱、1H NMR、13C NMR 和 MS 光谱分析阐明了合成共轭物的结构,结果表明数据与预期结构一致。利用正常细胞和参考药物紫杉醇评估了 9a-c、10a-c、11a-c 和 12a-c 对 HepG-2 和 HCT-116 癌细胞株的抗增殖活性。筛选结果表明,9b 和 9c 是对 HepG-2 和 HCT-116 癌细胞株最有效的共轭物,以紫杉醇为参照药物,其 IC50 分别为 8.49、9.52、16.87 和 21.75 µM。值得注意的是,与正常 Vero 细胞相比,9b 和 9c 对癌细胞的选择性更高。为了合理解释 9b 和 9c 的抗癌活性和选择性,我们针对人类拓扑异构酶 I 和 II 进行了分子对接研究,以更好地了解它们在原子水平上的抗癌活性。分子对接研究发现,平面吲哚喹啉融合四环和柔性侧链药噬体的存在共同提高了 DNA 介导和抑制 DNA 拓扑异构酶的活性。
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
CiteScore
4.40
自引率
8.30%
发文量
230
审稿时长
5.6 months
期刊介绍: JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.
期刊最新文献
Surfactant-modified carbon nano-onion-β-cyclodextrin nanocomposite as an efficient sorbent in dispersive solid phase extraction of metoprolol and atenolol from plasma samples prior to HPLC–PDA analysis Electrocatalytic reduction of nitrate using Mg(OH)2 copper modified electrode Core shell ZnO-MnO2 nanocomposites for dye degradation and DFT simulation An electrochemical sensor based on NH2-MWCNTS-CMC and ZIF-67 peroxidase-like nanocomposite for sensitive luteolin detection Experimental and computational insights into polymorphism in an antimicrobial sulfadrug: discovery of a novel monoclinic form of sulfamerazine
×
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