Serveur d'exploration Chloroquine

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Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.

Identifieur interne : 000070 ( PubMed/Curation ); précédent : 000069; suivant : 000071

Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.

Auteurs : Ziyang Guo [République populaire de Chine] ; Hailong Pei [République populaire de Chine] ; Jing Nie [République populaire de Chine] ; Wentao Hu [République populaire de Chine] ; Jian Zhang [République populaire de Chine] ; Jiahan Ding [République populaire de Chine] ; Shuxian Pan [République populaire de Chine] ; Bingyan Li [République populaire de Chine] ; Tom K. Hei [États-Unis] ; Weiqiang Chen [République populaire de Chine] ; Guangming Zhou [République populaire de Chine]

Source :

RBID : pubmed:30637976

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English descriptors

Abstract

Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.

DOI: 10.1111/cbdd.13477
PubMed: 30637976

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<term>Antineoplastic Agents (pharmacology)</term>
<term>Antineoplastic Agents (therapeutic use)</term>
<term>Cell Line, Tumor</term>
<term>Cell Survival (drug effects)</term>
<term>Chloroquine (chemistry)</term>
<term>Disease Models, Animal</term>
<term>G1 Phase Cell Cycle Checkpoints (drug effects)</term>
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<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles animaux de maladie humaine</term>
<term>Points de contrôle de la phase G1 du cycle cellulaire ()</term>
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<term>Triazines</term>
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<term>Cell Line, Tumor</term>
<term>Disease Models, Animal</term>
<term>Humans</term>
<term>Mice</term>
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<term>Animaux</term>
<term>Antinéoplasiques</term>
<term>Chloroquine</term>
<term>Humains</term>
<term>Lignée cellulaire tumorale</term>
<term>Modèles animaux de maladie humaine</term>
<term>Points de contrôle de la phase G1 du cycle cellulaire</term>
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<div type="abstract" xml:lang="en">Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.</div>
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<DateCompleted>
<Year>2020</Year>
<Month>02</Month>
<Day>27</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>02</Month>
<Day>27</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1747-0285</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>93</Volume>
<Issue>5</Issue>
<PubDate>
<Year>2019</Year>
<Month>05</Month>
</PubDate>
</JournalIssue>
<Title>Chemical biology & drug design</Title>
<ISOAbbreviation>Chem Biol Drug Des</ISOAbbreviation>
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<ArticleTitle>Anti-cancer effects of CQBTO, a chloroquine, and benzo(e)triazine oxide conjugate.</ArticleTitle>
<Pagination>
<MedlinePgn>874-882</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1111/cbdd.13477</ELocationID>
<Abstract>
<AbstractText Label="AIM">Autophagy is a self-protective process, and it confers cancer cells resistance against radio-chemotherapeutics. To induce cancer cell death, a series of compounds of 3-((4-((7-chloroquinolin-4-yl)amino)butyl)amino)-7-substituted benzo[e][1,2,4]triazine 1-oxide or CQBTO containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1-oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (CQ), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.</AbstractText>
<AbstractText Label="METHODS">In vitro cultured non-small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of CQBTO on cancer cells and toxicity to normal tissues. Cell viability was examined using the CCK8 assay. Genomic instability was determined with the cytochalasin B-blocked micronucleus assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Western blotting and immunofluorescence were used to detect the induction and localization of LC3, a biomarker for autophagy.</AbstractText>
<AbstractText Label="RESULTS">Compared with CQ, three CQBTO compounds were lethal to lung cancer cells, and CQBTO-3 was the most effective. The LD50 for CQBTO-3 was 21 μΜ in A549 cells and 21.5 μΜ in Calu-1 cells, which was lower than that of CQBTO-2 or CQBTO-1. Induction of LC3 foci and an increase in the LC3II/LC3I ratio demonstrated the induction of autophagy by CQBTO-3 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. CQBTO-3 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.</AbstractText>
<AbstractText Label="CONCLUSION">CQBTO-3 is a potential chemical compound for lung cancer treatment.</AbstractText>
<CopyrightInformation>© 2019 John Wiley & Sons A/S.</CopyrightInformation>
</Abstract>
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<LastName>Guo</LastName>
<ForeName>Ziyang</ForeName>
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<LastName>Pei</LastName>
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<Keyword MajorTopicYN="Y">lung cancer</Keyword>
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<Year>2018</Year>
<Month>12</Month>
<Day>11</Day>
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<Year>2018</Year>
<Month>12</Month>
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<ArticleId IdType="doi">10.1111/cbdd.13477</ArticleId>
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