{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T08:45:06Z","timestamp":1792226706983,"version":"4.4.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.bioorg.2020.104501","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T02:28:51Z","timestamp":1606184931000},"page":"104501","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"special_numbering":"C","title":["Design and development of Tetrahydro-Quinoline derivatives as dual mTOR-C1\/C2 inhibitors for the treatment of lung cancer"],"prefix":"10.1016","volume":"106","author":[{"given":"Udit J.","family":"Chaube","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Rawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek B.","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavesh","family":"Variya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hardik G.","family":"Bhatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2020.104501_b0005","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ctrv.2015.02.008","article-title":"Molecular histology of lung cancer: From targets to treatments","volume":"41","author":"Wood","year":"2015","journal-title":"Cancer Treat. Rev."},{"key":"10.1016\/j.bioorg.2020.104501_b0010","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nature09208","article-title":"Diverse somatic mutation patterns and pathway alterations in human cancers","volume":"466","author":"Kan","year":"2010","journal-title":"Nature."},{"key":"10.1016\/j.bioorg.2020.104501_b0015","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2012.08.024","article-title":"Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers","volume":"150","author":"Govindan","year":"2012","journal-title":"Cell."},{"key":"10.1016\/j.bioorg.2020.104501_b0020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.lungcan.2015.01.017","article-title":"Nicotine induces resistance to erlotinib via cross-talk between \u03b1 1 nAChR and EGFR in the non-small cell lung cancer xenograft model","volume":"88","author":"Li","year":"2015","journal-title":"Lung Cancer."},{"key":"10.1016\/j.bioorg.2020.104501_b0025","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1590\/S1807-59322011001100005","article-title":"Non-small cell lung cancer in never smokers: a clinical entity to be identified","volume":"66","author":"Santoro","year":"2011","journal-title":"Clinics."},{"key":"10.1016\/j.bioorg.2020.104501_b0030","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bcp.2014.05.011","article-title":"Targeting PI3K\/AKT\/mTOR pathway in non small cell lung cancer","volume":"90","author":"Fumarola","year":"2014","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bioorg.2020.104501_b0035","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.ejmech.2016.01.012","article-title":"PI3K\/AKT\/mTOR and Ras\/Raf\/MEK\/ERK signaling pathways inhibitors as anticancer agents: Structural and pharmacological perspectives","volume":"109","author":"Asati","year":"2016","journal-title":"Euro. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0040","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.ejmech.2014.04.051","article-title":"Synthesis of 5-substituted-1H-pyrazolo[4,3-d]pyrimidin-7(6H)-one analogs and their biological evaluation as anticancer agents: mTOR inhibitors","volume":"80","author":"Reddy","year":"2014","journal-title":"Euro. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0045","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.pharmthera.2013.12.004","article-title":"Molecular targets for cancer therapy in the PI3K\/AKT\/mTOR pathway","volume":"142","author":"Polivka","year":"2014","journal-title":"Pharmacol. Therapeut."},{"key":"10.1016\/j.bioorg.2020.104501_b0050","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.drudis.2011.02.008","article-title":"Targeting the mTOR kinase domain: the second generation of mTOR inhibitors","volume":"16","author":"Zhang","year":"2011","journal-title":"Drug Discov. Today."},{"key":"10.1016\/j.bioorg.2020.104501_b0055","first-page":"43","article-title":"Use of mTOR inhibitors in the treatment of breast cancer: an evaluation of factors that influence patient outcomes","volume":"6","author":"Jerusalem","year":"2014","journal-title":"Breast Cancer."},{"key":"10.1016\/j.bioorg.2020.104501_b0060","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/nature12122","article-title":"mTOR kinase structure, mechanism and regulation","volume":"497","author":"Yang","year":"2013","journal-title":"Nature."},{"key":"10.1016\/j.bioorg.2020.104501_b0065","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41422-018-0029-3","article-title":"Cryo-EM structure of human mTOR complex 2","volume":"28","author":"Chen","year":"2018","journal-title":"Cell Res."},{"key":"10.1016\/j.bioorg.2020.104501_b0070","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.bmcl.2015.12.075","article-title":"3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer","volume":"26","author":"Chaube","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"3","key":"10.1016\/j.bioorg.2020.104501_b0075","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s11030-017-9752-9","article-title":"3D-QSAR, molecular dynamics simulations, and molecular docking studies on pyridoaminotropanes and tetrahydroquinazoline as mTOR inhibitors","volume":"21","author":"Chaube","year":"2017","journal-title":"Mol. Divers."},{"key":"10.1016\/j.bioorg.2020.104501_b0080","doi-asserted-by":"crossref","first-page":"3758","DOI":"10.1016\/j.bmcl.2012.04.012","article-title":"Pharmacophore modeling, virtual screening and 3D-QSAR studies of 5-tetrahydroquinolinylidine aminoguanidine derivatives as sodium hydrogen exchanger inhibitors","volume":"22","author":"Bhatt","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.104501_b0085","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jtice.2015.07.024","article-title":"3D-QSAR studies on 5-hydroxy-6-oxo-1, 6-dihydropyrimidine-4-carboxamide derivatives as HIV-1 integrase inhibitors","volume":"59","author":"Patel","year":"2016","journal-title":"J. Taiwan Insti. Chem. Eng."},{"key":"10.1016\/j.bioorg.2020.104501_b0090","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejmech.2016.04.019","article-title":"Design, synthesis and anti-HIV activity of novel quinoxaline derivatives","volume":"117","author":"Patel","year":"2016","journal-title":"Euro. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0095","doi-asserted-by":"crossref","unstructured":"Matthews, N.; Kitao, A.; Laycock, S.; Hayward, S. Haptic-Assisted Interactive Molecular Docking Incorporating Receptor Flexibility. J. Chem. Inf. Model. [Online early access]. DOI: 10.1021\/acs.jcim.9b00112. Published Online: April 23, 2019.","DOI":"10.1021\/acs.jcim.9b00112"},{"key":"10.1016\/j.bioorg.2020.104501_b0100","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1021\/acs.jcim.8b00828","article-title":"Novel \u03b2-Keto\u2013Enol Pyrazolic Compounds as Potent Antifungal Agents. Design, Synthesis, Crystal Structure, DFT, Homology Modeling, and Docking Studies","volume":"59","author":"Tighadouini","year":"2019","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2020.104501_b0105","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/ejoc.201001459","article-title":"Synthesis of 6-Nitro-1,2,3,4-tetrahydroquinoline: An Experimental and Theoretical Study of Regioselective Nitration","volume":"2011","author":"Cordeiro","year":"2011","journal-title":"Euro. J. Org. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0110","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1021\/acs.jmedchem.5b00626","article-title":"Discovery of Mammalian Target of Rapamycin (mTOR) Kinase Inhibitor CC-223","volume":"58","author":"Mortensen","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0115","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1021\/acsmedchemlett.8b00002","article-title":"Discovery of Pyridopyrimidinones as Potent and Orally Active Dual Inhibitors of PI3K\/mTOR","volume":"9","author":"Yu","year":"2018","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2020.104501_b0120","doi-asserted-by":"crossref","first-page":"10285","DOI":"10.1039\/C5RA27017K","article-title":"Design and synthesis of potent N-phenylpyrimidine derivatives for the treatment of skin cancer","volume":"6","author":"Chaube","year":"2016","journal-title":"RSC Advances."},{"key":"10.1016\/j.bioorg.2020.104501_b0125","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1021\/np400518k","article-title":"Flavonoids, Flavonoid Metabolites, and Phenolic Acids Inhibit Oxidative Stress in the Neuronal Cell Line HT-22 Monitored by ECIS and MTT Assay: A Comparative Study","volume":"77","author":"Kling","year":"2014","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.bioorg.2020.104501_b0130","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1038\/s41598-017-01942-7","article-title":"Design, Synthesis and Biological Evaluation of novel Hedgehog Inhibitors for treating Pancreatic Cancer","volume":"7","author":"Kumar","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2020.104501_b0135","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1039\/C5OB02176F","article-title":"Design, synthesis and anticancer activities of novel otobain derivatives","volume":"14","author":"Li","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0140","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.ejmech.2017.03.020","article-title":"Scutellarin derivatives as apoptosis inducers: Design, synthesis and biological evaluation","volume":"135","author":"Han","year":"2017","journal-title":"Euro. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0145","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1021\/np400466j","article-title":"Napyradiomycin Derivatives, produced by a Marine-Derived Actinomycete, Illustrate Cytotoxicity by Induction of Apoptosis","volume":"77","author":"Farnaes","year":"2014","journal-title":"J. Nat. Prod."},{"key":"10.1016\/j.bioorg.2020.104501_b0150","doi-asserted-by":"crossref","first-page":"15016","DOI":"10.1038\/cddiscovery.2015.16","article-title":"mTORC2 controls cancer cell survival by modulating gluconeogenesis","volume":"1","author":"Khan","year":"2015","journal-title":"Cell Death Discov."},{"key":"10.1016\/j.bioorg.2020.104501_b0155","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1084\/jem.20141703","article-title":"PDK1 orchestrates early NK cell development through induction of E4BP4 expression and maintenance of IL-15 responsiveness","volume":"212","author":"Yang","year":"2015","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.bioorg.2020.104501_b0160","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1021\/acs.jmedchem.7b00357","article-title":"Design, Synthesis, and Biological Evaluation of Dimorpholine Substituted Thienopyrimidines as Potential Class I PI3K\/mTOR Dual Inhibitors","volume":"60","author":"Zhan","year":"2017","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0165","doi-asserted-by":"crossref","first-page":"5427","DOI":"10.1021\/acs.molpharmaceut.8b00996","article-title":"In Silico Discovery of a Small Molecule Suppressing Lung Carcinoma A549 Cells Proliferation and Inducing Autophagy via mTOR Pathway Inhibition","volume":"15","author":"Liu","year":"2018","journal-title":"Mol. Pharm."},{"key":"10.1016\/j.bioorg.2020.104501_b0170","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bioorg.2018.12.007","article-title":"A new class of diamide scaffold: Design, synthesis and biological evaluation as potent antimitotic agents, tubulin polymerization inhibition and apoptosis inducing activity studies","volume":"84","author":"Mohamed","year":"2019","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0175","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1158\/1078-0432.CCR-08-2057","article-title":"mTOR Inhibitor RAD001 (Everolimus) Has Antiangiogenic\/Vascular Properties Distinct from a VEGFR Tyrosine Kinase Inhibitor","volume":"15","author":"Lane","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.bioorg.2020.104501_b0180","doi-asserted-by":"crossref","first-page":"5498","DOI":"10.1021\/jm2005173","article-title":"Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines","volume":"54","author":"Bourderioux","year":"2011","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2020.104501_b0185","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.biopha.2016.05.042","article-title":"Antioxidant and antitumor efficacy of Luteolin, a dietary flavone on benzo(a)pyrene-induced experimental lung carcinogenesis","volume":"82","author":"Kasala","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.bioorg.2020.104501_b0190","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.cbi.2015.10.020","article-title":"Antiproliferative and antioxidant potential of hesperetin against benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice","volume":"242","author":"Bodduluru","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"10.1016\/j.bioorg.2020.104501_b0195","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.cccn.2004.07.004","article-title":"Protective effect of piperine on benzo(a)pyrene-induced lung carcinogenesis in Swiss albino mice","volume":"350","author":"Selvendiran","year":"2004","journal-title":"Clin. Chim. Acta."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820317995?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206820317995?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:13:48Z","timestamp":1758615228000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206820317995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":39,"alternative-id":["S0045206820317995"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.104501","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design and development of Tetrahydro-Quinoline derivatives as dual mTOR-C1\/C2 inhibitors for the treatment of lung cancer","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2020.104501","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104501"}}