Xinhang Zhang , Yashu Li , Yuchen Chen , Ziqi Liu , Zijin Li , Ziyin Wang , Yu Wang , Mingzhe Liu
{"title":"设计和合成具有双重功能的 NBD-荧光团并入的萘二亚胺衍生物作为 G-四链配体。","authors":"Xinhang Zhang , Yashu Li , Yuchen Chen , Ziqi Liu , Zijin Li , Ziyin Wang , Yu Wang , Mingzhe Liu","doi":"10.1016/j.bmcl.2024.129903","DOIUrl":null,"url":null,"abstract":"<div><p>Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds <strong>1NND</strong> and <strong>3NND</strong> exhibited fluorescent “turn-off” property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (<em>K</em><sub>d</sub>) of ligands against G4 by fluorescence titration method. Notably, the compound <strong>1NND</strong> not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC<sub>50</sub>) of 77.9 nM, but also exhibited high affinity against G4 with <em>K</em><sub>d</sub> of 1.72 μM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods.</p></div>","PeriodicalId":256,"journal":{"name":"Bioorganic & Medicinal Chemistry Letters","volume":"111 ","pages":"Article 129903"},"PeriodicalIF":2.5000,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design and synthesis of dual functional NBD-fluorophore-incorporated naphthalene diimide derivatives as G-quadruplex ligands\",\"authors\":\"Xinhang Zhang , Yashu Li , Yuchen Chen , Ziqi Liu , Zijin Li , Ziyin Wang , Yu Wang , Mingzhe Liu\",\"doi\":\"10.1016/j.bmcl.2024.129903\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds <strong>1NND</strong> and <strong>3NND</strong> exhibited fluorescent “turn-off” property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (<em>K</em><sub>d</sub>) of ligands against G4 by fluorescence titration method. Notably, the compound <strong>1NND</strong> not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC<sub>50</sub>) of 77.9 nM, but also exhibited high affinity against G4 with <em>K</em><sub>d</sub> of 1.72 μM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods.</p></div>\",\"PeriodicalId\":256,\"journal\":{\"name\":\"Bioorganic & Medicinal Chemistry Letters\",\"volume\":\"111 \",\"pages\":\"Article 129903\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic & Medicinal Chemistry Letters\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0960894X24003056\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic & Medicinal Chemistry Letters","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0960894X24003056","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design and synthesis of dual functional NBD-fluorophore-incorporated naphthalene diimide derivatives as G-quadruplex ligands
Nitrobenzoxadiazole (NBD)-incorporated naphthalene diimide derivatives were designed and synthesized as candidates of antitumor agents with cytotoxicity against human pancreatic cancer cell MIA PaCa-2. Among these, compounds 1NND and 3NND exhibited fluorescent “turn-off” property toward human telomeric G-quadruplex (G4), which allows the direct measurement of dissociation constant (Kd) of ligands against G4 by fluorescence titration method. Notably, the compound 1NND not only exhibited great cytotoxic activity against MIA PaCa-2 with a half maximal inhibitory concentration (IC50) of 77.9 nM, but also exhibited high affinity against G4 with Kd of 1.72 μM. Furthermore, the target binding properties were investigated by circular dichroism (CD) spectra and further studied by molecular docking methods.
期刊介绍：
Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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