{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:21Z","timestamp":1783123221030,"version":"3.54.6"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2017T100399"],"award-info":[{"award-number":["2017T100399"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Autophagy is a self\u2010protective process, and it confers cancer cells resistance against radio\u2010chemotherapeutics. To induce cancer cell death, a series of compounds of 3\u2010((4\u2010((7\u2010chloroquinolin\u20104\u2010yl)amino)butyl)amino)\u20107\u2010substituted benzo[e][1,2,4]triazine 1\u2010oxide or <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content> containing two critical chemical groups were designed and synthesized. One compound, benzo[e][1,2,4]triazine 1\u2010oxide, yielded free radicals to trigger autophagy, and the other one, chloroquine (<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>), was an inhibitor of autophagy. We hypothesized that the compounds could kill cancer cells effectively by inducing incomplete autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In vitro cultured non\u2010small cell lung carcinoma cells and primary lung tumors in mice in vivo were used to test the lethal effects of <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content> on cancer cells and toxicity to normal tissues. Cell viability was examined using the <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>8 assay. Genomic instability was determined with the cytochalasin B\u2010blocked 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 <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3, a biomarker for autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with <jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>, three <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content> compounds were lethal to lung cancer cells, and <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20103 was the most effective. The <jats:styled-content style=\"fixed-case\">LD<\/jats:styled-content>50 for <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20103 was 21\u00a0\u03bc\u039c in A549 cells and 21.5\u00a0\u03bc\u039c in Calu\u20101 cells, which was lower than that of <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20102 or <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20101. Induction of <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3 foci and an increase in the <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3I ratio demonstrated the induction of autophagy by <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20103 in A549 cells, whereas no obvious micronuclei or cell cycle arrest was observed. No detectable toxicity to normal mice was observed. <jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20103 improved the quality of mouse life, reduced the number and size of existing tumors, and suppressed tumor formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">CQBTO<\/jats:styled-content>\u20103 is a potential chemical compound for lung cancer treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cbdd.13477","type":"journal-article","created":{"date-parts":[[2019,1,14]],"date-time":"2019-01-14T07:43:09Z","timestamp":1547451789000},"page":"874-882","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti\u2010cancer effects of <scp>CQBTO<\/scp>, a chloroquine, and benzo(e)triazine oxide conjugate"],"prefix":"10.1111","volume":"93","author":[{"given":"Ziyang","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Pei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Nie","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wentao","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahan","family":"Ding","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxian","family":"Pan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingyan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Institute of Space Life Sciences Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions Medical College of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom K.","family":"Hei","sequence":"additional","affiliation":[{"name":"Center for Radiological Research College of Physician and Surgeons Columbia University  New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Modern Physics Chinese Academy of Sciences  Lanzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5695-2308","authenticated-orcid":false,"given":"Guangming","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Radiation Medicine and 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