{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:48:25Z","timestamp":1761238105074,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T00:00:00Z","timestamp":1402444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>As part of our program to identify novel secondary metabolites that target  drug-resistant ovarian cancers, a screening of our aquatic-derived actinomycete fraction library against a cisplatin-resistant ovarian cancer cell line (OVCAR5) led to the isolation of novel diaza-anthracene antibiotic diazaquinomycin E (DAQE; 1), the isomeric mixture of diazaquinomycin F (DAQF; 2) and diazaquinomycin G (DAQG; 3), and known analog diazaquinomycin A (DAQA; 4). The structures of DAQF and DAQG were solved through deconvolution of X-Ray diffraction data of their corresponding co-crystal. DAQE and DAQA exhibited moderate LC50 values against OVCAR5 of 9.0 and 8.8 \u03bcM, respectively. At lethal concentrations of DAQA, evidence of DNA damage was observed via induction of apoptosis through cleaved-PARP. Herein, we will discuss the isolation, structure elucidation, and biological activity of these secondary metabolites.<\/jats:p>","DOI":"10.3390\/md12063574","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T11:59:22Z","timestamp":1402487962000},"page":"3574-3586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Diazaquinomycins E\u2013G, Novel Diaza-Anthracene Analogs from a Marine-Derived Streptomyces sp."],"prefix":"10.3390","volume":"12","author":[{"given":"Michael","family":"Mullowney","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eoghain\u00edn","family":"\u00d3 hAinmhire","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anam","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Tanouye","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Santarsiero","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Burdette","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Murphy","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL 60612, USA"},{"name":"Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago,  IL 60607, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1021\/np200906s","article-title":"Natural products as sources of new drugs over the 30 years from 1981 to 2010","volume":"75","author":"Newman","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3322\/caac.21208","article-title":"Cancer statistics, 2014","volume":"64","author":"Siegel","year":"2014","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S1470-2045(02)00846-X","article-title":"Part I: Chemotherapy for epithelial ovarian cancer-treatment at first diagnosis","volume":"3","author":"Harries","year":"2002","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1470-2045(02)00847-1","article-title":"Part II: Chemotherapy for epithelial ovarian cancer-treatment of recurrent disease","volume":"3","author":"Harries","year":"2002","journal-title":"Lancet Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.1016\/S0040-4039(00)88190-3","article-title":"The structures of diazaquinomycins A and B, new antibiotic metabolites","volume":"24","author":"Omura","year":"1983","journal-title":"Tetrahedron Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1080\/14786410410001704741","article-title":"Isolation and structure elucidation of diazaquinomycin C from a terrestrial Streptomyces sp. and confirmation of the akashin structure","volume":"19","author":"Maskey","year":"2005","journal-title":"Nat. Prod. Res."},{"key":"ref_7","first-page":"125","article-title":"XDS","volume":"66","author":"Kabsch","year":"2010","journal-title":"Acta Crystallogr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1107\/S0108767307043930","article-title":"A short history of SHELX","volume":"64","author":"Sheldrick","year":"2008","journal-title":"Acta Crystallogr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.7164\/antibiotics.35.1425","article-title":"OM-704 A, A new antibiotic active against gram-positive bacteria produced by Streptomyces sp","volume":"35","author":"Omura","year":"1982","journal-title":"J. Antibiot."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.7164\/antibiotics.38.1025","article-title":"Diazaquinomycin A, a new antifolate antibiotic, inhibits thymidylate synthase","volume":"38","author":"Murata","year":"1985","journal-title":"J. Antibiot."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.7164\/antibiotics.42.727","article-title":"Synthesis and biological activity of analogues of diazaquinomycin A, a new thymidylate synthase inhibitor","volume":"42","author":"Tsuzuki","year":"1989","journal-title":"J. Anitbiot."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1099\/ijs.0.019091-0","article-title":"Streptomyces coacervatus sp. nov., isolated from the intestinal tract of Armadillidium vulgare","volume":"61","author":"Shibazaki","year":"2011","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337:1","DOI":"10.1186\/1471-2164-13-337","article-title":"Genomic and transcriptomic insights into the thermo-regulated biosynthesis of validamycin in Streptomyces hygroscopicus 5008","volume":"13","author":"Wu","year":"2012","journal-title":"BMC Genomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e01147","DOI":"10.1128\/genomeA.01147-13","article-title":"Draft genome sequence of Streptomyces roseochromogenes subsp. oscitans DS 12.976, producer of the aminocoumarin antibiotic clorobiocin","volume":"2","author":"Ruckert","year":"2014","journal-title":"Genome Announc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B colorimetric assay for cytotoxicity screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e89553","DOI":"10.1371\/journal.pone.0089553","article-title":"Mutation or Loss of p53 Differentially Modifies TGFbeta Action in Ovarian Cancer","volume":"9","author":"Quartuccio","year":"2014","journal-title":"PLoS One"}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/6\/3574\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:12:21Z","timestamp":1760217141000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/12\/6\/3574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,11]]},"references-count":16,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2014,6]]}},"alternative-id":["md12063574"],"URL":"https:\/\/doi.org\/10.3390\/md12063574","relation":{},"ISSN":["1660-3397"],"issn-type":[{"type":"electronic","value":"1660-3397"}],"subject":[],"published":{"date-parts":[[2014,6,11]]}}}