{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:32:43Z","timestamp":1790188363731,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T00:00:00Z","timestamp":1540425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81502935"],"award-info":[{"award-number":["81502935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Rapamycin is an mTOR allosteric inhibitor with multiple functions such as immunosuppressive, anticancer, and lifespan prolonging activities. Its C\u201043 semi\u2010synthetic derivatives temsirolimus and everolimus have been used as mTOR targeting anticancer drugs in the clinic. Following our previous research on antitumor rapalogs modified on the C\u201043 position, 13 novel rapamycin triazole hybrids (<jats:bold>6a\u2013g<\/jats:bold>, <jats:bold>7a\u2013f<\/jats:bold>) were designed and synthesized on the C\u201028 position of rapamycin via Huisgen's reaction. Anticancer assays indicated that the targeted derivatives containing phenyl and 4\u2010methylphenyl groups showed an obvious raise in anticancer activity. On the contrary, the compounds with methoxyl, amine, and halogen groups on the benzene ring displayed lower anticancer activity. Compound <jats:bold>6c<\/jats:bold>, as the most active compound, showed a stronger inhibition effect as compared with rapamycin for almost all of the tested cell lines (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01), except PC\u20103. Meanwhile, the effect of <jats:bold>6c<\/jats:bold> on inducing apoptosis and cell cycle arrest in A549 cells was more powerful than that of rapamycin. In addition, <jats:bold>6c<\/jats:bold> inhibited the phosphorylation of mTOR and its downstream key kinases 4EBP1 and p70S6K1 in A549 cells, indicating that <jats:bold>6c<\/jats:bold> also effectively inhibits the mTORC1 signaling pathway as rapamycin. On the basis of these findings, <jats:bold>6c<\/jats:bold> may have the potential to be developed as a new mTOR inhibitor against specific cancers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201800123","type":"journal-article","created":{"date-parts":[[2018,10,25]],"date-time":"2018-10-25T11:59:36Z","timestamp":1540468776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synthesis and anticancer activity of novel rapamycin C\u201028 containing triazole moiety compounds"],"prefix":"10.1002","volume":"351","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8999-1215","authenticated-orcid":false,"given":"Qingwen","family":"Huang","sequence":"first","affiliation":[{"name":"Fujian University of Traditional Chinese Medicine Fuzhou P. R. China"},{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Xie","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubing","family":"Lv","sequence":"additional","affiliation":[{"name":"Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd. Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XueHui","family":"Huang","sequence":"additional","affiliation":[{"name":"Hangzhou Huadong Medicine Group Pharmaceutical Research Institute Co. Ltd. Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Ying","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congshen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanrong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Fujian University of Traditional Chinese Medicine Fuzhou P. R. China"},{"name":"Fujian Provincial Key Laboratory of Screening for Novel Microbial Products Fujian Institute of Microbiology Fuzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.721"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.727"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700498200"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12122"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.05284-11"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2012.04004.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.22441"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25559"},{"key":"e_1_2_7_10_1","first-page":"1772","volume":"6","author":"Imrali A.","year":"2016","journal-title":"Am. J. Cancer Res"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-470X(10)80014-X"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12109"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2017.4901"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08221"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.16351"},{"key":"e_1_2_7_16_1","first-page":"4","volume":"314","author":"Van Skike C. S.","year":"2017","journal-title":"Am. J. Physiol. Heart Circ. Physiol"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1677-1"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066838"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.5482"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1109653"},{"key":"e_1_2_7_21_1","first-page":"1872","volume":"364","author":"Castellano D.","year":"2011","journal-title":"N. Engl. J. Med"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201500457"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c15-01016"},{"key":"e_1_2_7_24_1","first-page":"224","volume":"11","author":"Yang D.","year":"2016","journal-title":"Chin. Med. Biotechnol"},{"key":"e_1_2_7_25_1","unstructured":"F.Nan J.Ding J.Zuo(Shanghai Institute of Materia Medica Chinese Academy of Sciences CN). WO 2010\/031251 A1."}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fardp.201800123","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.201800123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:57:16Z","timestamp":1694933836000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.201800123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,25]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/ardp.201800123"],"URL":"https:\/\/doi.org\/10.1002\/ardp.201800123","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,25]]},"assertion":[{"value":"2018-04-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"1800123"}}