{"corpus_id":34133193,"paper_sha":"de19e1b24d7a1d0e15b3fc9b673ba7fa695fccab","doi":"10.1016/j.ejmech.2017.01.025","arxiv_id":null,"pmid":28157593,"pmcid":null,"mag_id":2581371435,"dblp_id":null,"acl_id":null,"title":"Naphthalene diimide-polyamine hybrids as antiproliferative agents: Focus on the architecture of the polyamine chains.","year":2017,"publication_date":"2017-03-10","venue":"European journal of medicinal chemistry","journal":{"name":"European journal of medicinal chemistry","pages":"\n          107-122\n        ","volume":"128"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article"],"s2_fields_of_study":["Medicine","Chemistry"],"reference_count":33,"citation_count":16,"influential_citation_count":0,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Antineoplastic Agents","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D000970"},{"d":"Cell Cycle","mj":false,"qs":[{"q":"drug effects","mj":false,"ui":"Q000187"}],"ui":"D002453"},{"d":"Cell Survival","mj":false,"qs":[{"q":"drug effects","mj":true,"ui":"Q000187"}],"ui":"D002470"},{"d":"DNA","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D004247"},{"d":"DNA Topoisomerases, Type II","mj":false,"qs":[{"q":"chemistry","mj":false,"ui":"Q000737"}],"ui":"D004250"},{"d":"Drug Screening Assays, Antitumor","mj":false,"ui":"D004354"},{"d":"Flow Cytometry","mj":false,"ui":"D005434"},{"d":"G-Quadruplexes","mj":false,"ui":"D054856"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Imides","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D007094"},{"d":"Jurkat Cells","mj":false,"ui":"D019169"},{"d":"Models, Molecular","mj":false,"ui":"D008958"},{"d":"Naphthalenes","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D009281"},{"d":"Neoplasms","mj":false,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D009369"},{"d":"Phenanthrolines","mj":false,"qs":[{"q":"pharmacology","mj":true,"ui":"Q000494"}],"ui":"D010618"},{"d":"Polyamines","mj":false,"qs":[{"q":"chemistry","mj":true,"ui":"Q000737"}],"ui":"D011073"},{"d":"Taq Polymerase","mj":false,"qs":[{"q":"antagonists & inhibitors","mj":false,"ui":"Q000037"}],"ui":"D019914"}],"chemicals":[{"n":"2-(3-((4-aminobutyl )amino)propyl )-7-(3-((2-methoxybenzyl)amino)propyl)benzo(lmn)(3,8)phenanthroline-1,3,6,8(2H,7H)-tetraone","ui":"C000616873","reg":"0"},{"n":"Antineoplastic Agents","ui":"D000970","reg":"0"},{"n":"Imides","ui":"D007094","reg":"0"},{"n":"Naphthalenes","ui":"D009281","reg":"0"},{"n":"Phenanthrolines","ui":"D010618","reg":"0"},{"n":"Polyamines","ui":"D011073","reg":"0"},{"n":"naphthalenediimide","ui":"C542131","reg":"22291-04-9"},{"n":"DNA","ui":"D004247","reg":"9007-49-2"},{"n":"Taq Polymerase","ui":"D019914","reg":"EC 2.7.7.-"},{"n":"DNA Topoisomerases, Type II","ui":"D004250","reg":"EC 5.99.1.3"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"http://www.elsevier.com/journals/european-journal-of-medicinal-chemistry/0223-5234?generatepdf=true","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/de19e1b24d7a1d0e15b3fc9b673ba7fa695fccab","s2_open_access_license":"CCBYNCND","s2_open_access_status":"GREEN","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"Naphthalene diimides (NDIs) have been widely used as scaffold to design DNA-directed agents able to target peculiar DNA secondary arrangements endowed with relevant biochemical roles. Recently, we have reported disubstituted linear- and macrocyclic-NDIs that bind telomeric and non-telomeric G-quadruplex with high degree of affinity and selectivity. Herein, the synthesis, biological evaluation and molecular modelling studies of a series of asymmetrically substituted NDIs are reported. Among these, compound 9 emerges as the most interesting of the series being able to bind telomeric G-quadruplex (ΔTm = 29 °C at 2.5 μM), to inhibit the activity of DNA processing enzymes, such as topoisomerase II and TAQ-polymerase, and to exert antiproliferative effects in the NCI panel of cancer cell lines with GI50 values in the micro-to nanomolar concentration range (i.e. SR cell line, GI50 = 76 nM). Molecular mechanisms of cell death have been investigated and molecular modelling studies have been performed in order to shed light on the antiproliferative and DNA-recognition processes.","claims":[{"public_id":"cl_0de29ff1dc29cec3b2a9e9ce5894e6ae","status":"active","text":"A series of asymmetrically substituted naphthalene diimides was synthesized, biologically evaluated, and examined by molecular modelling.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_0de29ff1dc29cec3b2a9e9ce5894e6ae"},{"public_id":"cl_4f75c7f8537e7dd1910fe1f5f608249b","status":"active","text":"Compound 9 binds telomeric G-quadruplex with a ΔTm of 29 °C at 2.5 μM, inhibits topoisomerase II and TAQ-polymerase, and shows antiproliferative activity across the NCI cancer cell line panel with GI50 values in the micro- to nanomolar range, including 76 nM in the SR cell line.","confidence":0.97,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_4f75c7f8537e7dd1910fe1f5f608249b"},{"public_id":"cl_a63756d1df5e8dd45475f8f952bdad2c","status":"active","text":"Compound 9 is the most promising compound in the series.","confidence":0.89,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_a63756d1df5e8dd45475f8f952bdad2c"},{"public_id":"cl_2a39b295f165b3f31f8113f0d540e1d3","status":"active","text":"Molecular mechanisms of cell death and DNA-recognition processes were investigated to explain the antiproliferative activity.","confidence":0.86,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous 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