{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:08:25Z","timestamp":1791295705755,"version":"4.1.0"},"reference-count":85,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,9,1]],"date-time":"2019-09-01T00:00:00Z","timestamp":1567296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"publisher","award":["20170540858"],"award-info":[{"award-number":["20170540858"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21502121"],"award-info":[{"award-number":["21502121"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21772124"],"award-info":[{"award-number":["21772124"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007620","name":"Department of Education of Liaoning Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2019,9]]},"DOI":"10.1016\/j.ejmech.2019.06.016","type":"journal-article","created":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T21:50:11Z","timestamp":1559771411000},"page":"446-457","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Hydrogen sulfide donating ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane derivatives: Design, synthesis and antiproliferative properties"],"prefix":"10.1016","volume":"178","author":[{"given":"Haonan","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5705-6377","authenticated-orcid":false,"given":"Shengtao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Uchita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-0402","authenticated-orcid":false,"given":"Jinyi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6964-4619","authenticated-orcid":false,"given":"Dahong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2019.06.016_bib1","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/nchem.2479","article-title":"Counting on natural products for drug design","volume":"8","author":"Rodrigues","year":"2016","journal-title":"Nat. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib2","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural products as sources of new drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib3","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1021\/acs.jnatprod.5b00802","article-title":"Bioactive enmein-type ent-kaurane diterpenoids from Isodon phyllostachys","volume":"79","author":"Yang","year":"2016","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib4","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1021\/np100110u","article-title":"Cytotoxic ent-kaurane diterpenoids from Isodon rubescens var. lushiensis","volume":"73","author":"Luo","year":"2010","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib5","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1021\/np0705965","article-title":"ent-Kaurane diterpenoids from Isodon japonicus","volume":"71","author":"Hong","year":"2008","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib6","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1021\/ol3013205","article-title":"Ternifolide A, a new diterpenoid rossessing a rare macrolide motif from Isodon ternifolius","volume":"14","author":"Zou","year":"2012","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib7","doi-asserted-by":"crossref","first-page":"4727","DOI":"10.1021\/ol061757j","article-title":"A\u00a0cytotoxic diterpene from Isodon eriocalyx with a unique skeleton","volume":"8","author":"Han","year":"2006","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib8","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1021\/np200140j","article-title":"Structure and cytotoxicity of diterpenoids from Isodon adenolomus","volume":"74","author":"Zhao","year":"2011","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib9","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1021\/ol200086k","article-title":"Rubesanolides A and B: diterpenoids from Isodon rubescens","volume":"13","author":"Zou","year":"2011","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib10","first-page":"1302","article-title":"New Bicyclo[3.1.0]hexane unit ent-kaurane diterpene and its seco-derivative from Isodon eriocalyx var","volume":"14","author":"Wang","year":"2012","journal-title":"laxiflora, Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib11","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1016\/j.bmcl.2008.06.097","article-title":"Synthesis and biological evaluation of novel 1-O- and 14-O-derivatives of oridonin as potential anticancer drug candidates","volume":"18","author":"Xu","year":"2008","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.06.016_bib12","doi-asserted-by":"crossref","first-page":"7556","DOI":"10.3390\/molecules17067556","article-title":"Synthesis and biological evaluation of novel furozan-based nitric oxide-releasing derivatives of oridonin as potential anti-tumor agents","volume":"17","author":"Li","year":"2012","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2019.06.016_bib13","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1021\/ol4015865","article-title":"Overcoming synthetic challenges of oridonin A-ring structural diversification: regio- and stereoselective installation of azides and 1,2,3-triazoles at the C-1, C-2, or C-3 position","volume":"15","author":"Ding","year":"2013","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib14","doi-asserted-by":"crossref","first-page":"8814","DOI":"10.1021\/jm401248x","article-title":"Oridonin ring A-based diverse constructions of enone functionality: identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis","volume":"56","author":"Ding","year":"2013","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib15","doi-asserted-by":"crossref","first-page":"5048","DOI":"10.1021\/jm400367n","article-title":"Novel nitrogen-enriched oridonin analogues with thiazole-fused A-ring: protecting group-free synthesis, enhanced anticancer profile, and improved aqueous solubility","volume":"56","author":"Ding","year":"2013","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1021\/ml500141f","article-title":"Novel hybrids of natural oridonin-bearing nitrogen mustards as potential anticancer drug candidates","volume":"5","author":"Xu","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib17","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.1016\/j.bmcl.2014.04.119","article-title":"Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives","volume":"24","author":"Xu","year":"2014","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.06.016_bib18","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1021\/acs.jmedchem.6b01652","article-title":"A\u00a0novel potent anticancer compound optimized from a natural oridonin scaffold induces apoptosis and cell cycle arrest through the mitochondrial pathway","volume":"60","author":"Xu","year":"2017","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib19","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.ejmech.2016.06.015","article-title":"Discovery and development of natural product oridonin-inspired anticancer agents","volume":"122","author":"Ding","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib20","doi-asserted-by":"crossref","first-page":"575","DOI":"10.3390\/molecules21050575","article-title":"Antitumor and antibacterial derivatives of oridonin: a main composition of Dong-Ling-Cao","volume":"21","author":"Li","year":"2016","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2019.06.016_bib21","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1039\/j39700001674","article-title":"Terpenoids. Part XV. Structure and absolute configuration oridonin isolated from Isodon japonicus and Isodon trichocarpus","volume":"21","author":"Fujita","year":"1970","journal-title":"J.\u00a0Chem. Soc. C"},{"key":"10.1016\/j.ejmech.2019.06.016_bib22","doi-asserted-by":"crossref","first-page":"3441","DOI":"10.1182\/blood-2006-06-032250","article-title":"Oridonin, a diterpenoid extracted from medicinal herbs, targets AML1-ETO fusion protein and shows potent antitumor activity with low adverse effects on t(8;21) leukemia in\u00a0vitro and in\u00a0vivo","volume":"109","author":"Zhou","year":"2007","journal-title":"Blood"},{"key":"10.1016\/j.ejmech.2019.06.016_bib23","first-page":"1793","article-title":"Oridonin nanosuspension was more effective than free oridonin on G2\/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line","volume":"7","author":"Qi","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"10.1016\/j.ejmech.2019.06.016_bib24","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41419-017-0031-6","article-title":"Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-\u03b3 and inhibiting Nrf2 pathway","volume":"9","author":"Lu","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2019.06.016_bib25","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1038\/cddis.2017.35","article-title":"Oridonin induces autophagy via inhibition of glucose metabolism in p53-mutated colorectal cancer cells","volume":"8","author":"Yao","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2019.06.016_bib26","doi-asserted-by":"crossref","first-page":"2701","DOI":"10.1038\/cddis.2017.121","article-title":"Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs","volume":"8","author":"Zhou","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2019.06.016_bib27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1186\/s13045-016-0303-0","article-title":"Synergistic effect of oridonin and a PI3K\/mTOR inhibitor on the non-germinal center B cell-like subtype of diffuse large B cell lymphoma","volume":"9","author":"Qing","year":"2016","journal-title":"J.\u00a0Hematol. Oncol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib28","doi-asserted-by":"crossref","first-page":"10588","DOI":"10.1002\/anie.201404482","article-title":"The total synthesis of Isodon diterpenes","volume":"53","author":"Lazarski","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2019.06.016_bib29","doi-asserted-by":"crossref","first-page":"9425","DOI":"10.1021\/jacs.6b06623","article-title":"11-Step total synthesis of (-)-Maoecrystal V","volume":"138","author":"Cernijenko","year":"2016","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2019.06.016_bib30","doi-asserted-by":"crossref","first-page":"11764","DOI":"10.1021\/ja406599a","article-title":"A\u00a0unified strategy to ent-kauranoid natural products: total syntheses of (-)-trichorabdal A and (-)-longikaurin E","volume":"135","author":"Yeoman","year":"2013","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2019.06.016_bib31","doi-asserted-by":"crossref","first-page":"14964","DOI":"10.1021\/ja2073356","article-title":"A\u00a0concise total synthesis of (-)-maoecrystal Z","volume":"133","author":"Cha","year":"2011","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2019.06.016_bib32","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1002\/anie.201310060","article-title":"Total synthesis of the Isodon diterpene sculponeatin N","volume":"53","author":"Moritz","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2019.06.016_bib33","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1021\/np900406c","article-title":"ent-Kaurane and cembrane diterpenoids from Isodon sculponeatus and their cytotoxicity","volume":"72","author":"Li","year":"2009","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib34","doi-asserted-by":"crossref","first-page":"7445","DOI":"10.1016\/j.tet.2014.08.018","article-title":"6,7-Seco-ent-kaurane-type diterpenoids from Isodon eriocalyx var. laxiflora","volume":"70","author":"Wang","year":"2014","journal-title":"Tetrahedron"},{"key":"10.1016\/j.ejmech.2019.06.016_bib35","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1039\/b604174d","article-title":"Diterpenoids from Isodon species and their biological activities","volume":"23","author":"Sun","year":"2006","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.ejmech.2019.06.016_bib36","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1039\/C7NP00027H","article-title":"Diterpenoids from Isodon species: an update","volume":"34","author":"Liu","year":"2017","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.ejmech.2019.06.016_bib37","doi-asserted-by":"crossref","first-page":"2914","DOI":"10.3390\/molecules23112914","article-title":"Bioactive natural spirolactone-type 6,7-seco-ent-kaurane diterpenoids and synthetic derivatives","volume":"23","author":"Li","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2019.06.016_bib38","doi-asserted-by":"crossref","first-page":"9773","DOI":"10.1002\/chem.201802083","article-title":"Total syntheses of trichorabdal A and maoecrystal Z","volume":"24","author":"Lv","year":"2018","journal-title":"Chem. Eur J."},{"key":"10.1016\/j.ejmech.2019.06.016_bib39","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/nchembio.2007.1","article-title":"Modern synthetic efforts toward biologically active terpenes","volume":"3","author":"Maimone","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib40","doi-asserted-by":"crossref","first-page":"270","DOI":"10.3390\/molecules23020270","article-title":"Novel strategies using total gastrodin and gastrodigenin, or total gastrodigenin for quality control of gastrodia elata","volume":"23","author":"Tang","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2019.06.016_bib41","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.3390\/molecules22071137","article-title":"Analytical techniques and pharmacokinetics of gastrodia elata blume and its constituents","volume":"22","author":"Wu","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2019.06.016_bib42","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.phytol.2017.04.035","article-title":"Identification, characterization and in\u00a0vitro neuroprotection of N6-(4-hydroxybenzyl) adenine riboside and its metabolites","volume":"20","author":"Tang","year":"2017","journal-title":"Phytochem. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib43","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.bmc.2016.12.045","article-title":"Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities","volume":"25","author":"Meka","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib44","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ejmech.2017.09.014","article-title":"Natural isoflavone biochanin A as a template for the design of new and potent 3-phenylquinolone efflux inhibitors against mycobacterium avium","volume":"140","author":"Cannalire","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib45","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.ejmech.2017.09.004","article-title":"Structure-based design, synthesis, and biological evaluation of withaferin A-analogues as potent apoptotic inducers","volume":"140","author":"Llanos","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib46","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ejmech.2017.09.046","article-title":"Discovery and synthesis of novel Wogonin derivatives with potent antitumor activity in\u00a0vitro","volume":"140","author":"Wang","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib47","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":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib48","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.ejmech.2017.09.041","article-title":"Synthesis and antiproliferative properties of new hydrophilic esters of triterpenic acids","volume":"140","author":"Eignerova","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.ejmech.2017.05.018","article-title":"Nitric oxide-releasing derivatives of brefeldin A as potent and highly selective anticancer agents","volume":"136","author":"Tian","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib50","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ejmech.2012.03.024","article-title":"The conversion of oridonin to spirolactone-type or enmein-type diterpenoid: synthesis and biological evaluation of ent-6,7-seco-oridonin derivatives as novel potential anticancer agents","volume":"52","author":"Wang","year":"2012","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib51","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.ejmech.2012.11.002","article-title":"Synthesis of spirolactone-type diterpenoid derivatives from kaurene-type oridonin with improved antiproliferative effects and their apoptosis-inducing activity in human hepatoma Bel-7402 cells","volume":"59","author":"Li","year":"2013","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib52","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1016\/j.bmcl.2016.07.059","article-title":"Novel nitric oxide-releasing spirolactone-type diterpenoid derivatives with in\u00a0vitro synergistic anticancer activity as apoptosis inducer","volume":"26","author":"Li","year":"2016","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.ejmech.2019.06.016_bib53","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1021\/acs.jnatprod.7b00057","article-title":"6,7-Seco-ent-kauranoids derived from oridonin as potential anticancer agents","volume":"80","author":"Xu","year":"2017","journal-title":"J.\u00a0Nat. Prod."},{"key":"10.1016\/j.ejmech.2019.06.016_bib54","doi-asserted-by":"crossref","first-page":"7256","DOI":"10.1021\/jacs.6b03780","article-title":"Self-immolative thiocarbamates provide access to triggered H2S donors and analyte replacement fluorescent probes","volume":"138","author":"Steiger","year":"2016","journal-title":"J.\u00a0Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2019.06.016_bib55","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1089\/ars.2016.6909","article-title":"Gasotransmitter heterocellular signaling","volume":"26","author":"Kolluru","year":"2017","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejmech.2019.06.016_bib56","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nrd4433","article-title":"Hydrogen sulfide-based therapeutics: exploiting a unique but ubiquitous gasotransmitter","volume":"14","author":"Wallace","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2019.06.016_bib57","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrd.2015.1","article-title":"Gasotransmitters in cancer: from pathophysiology to experimental therapy","volume":"15","author":"Szabo","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2019.06.016_bib58","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1042\/CS20110267","article-title":"Emerging role of hydrogen sulfide in health and disease: critical appraisal of biomarkers and pharmacological tools","volume":"121","author":"Whiteman","year":"2011","journal-title":"Clin. Sci."},{"key":"10.1016\/j.ejmech.2019.06.016_bib59","first-page":"1","article-title":"Role of hydrogen sulfide in ischemia-reperfusion injury","volume":"2015","author":"Wu","year":"2015","journal-title":"Oxid. Med. Cell Longev"},{"key":"10.1016\/j.ejmech.2019.06.016_bib60","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1097\/HJH.0000000000001605","article-title":"Hydrogen sulfide improves endothelial dysfunction in hypertension by activating peroxisome proliferator-activated receptor delta\/endothelial nitric oxide synthase signaling","volume":"36","author":"Xiao","year":"2018","journal-title":"J.\u00a0Hypertens."},{"key":"10.1016\/j.ejmech.2019.06.016_bib61","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1089\/ars.2013.5324","article-title":"Hydrogen sulfide and the pathogenesis of atherosclerosis, Antioxid","volume":"20","author":"Mani","year":"2014","journal-title":"Redox Signal"},{"key":"10.1016\/j.ejmech.2019.06.016_bib62","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.jmb.2016.12.015","article-title":"Functional and molecular insights of hydrogen sulfide signaling and protein sulfhydration","volume":"429","author":"Sen","year":"2017","journal-title":"J.\u00a0Mol. Biol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib63","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/path.4659","article-title":"Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology","volume":"238","author":"Carter","year":"2016","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib64","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1124\/pr.117.014050","article-title":"International union of basic and clinical pharmacology. CII: pharmacological modulation of H2S Levels: H2S donors and H2S biosynthesis inhibitors","volume":"69","author":"Szabo","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.ejmech.2019.06.016_bib65","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/sj.bjp.0706014","article-title":"Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis","volume":"143","author":"Mok","year":"2004","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib66","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1038\/s41598-017-05457-z","article-title":"Hydrogen sulfide acts as a double-edged sword in human hepatocellular carcinoma cells through EGFR\/ERK\/MMP-2 and PTEN\/AKT signaling pathways","volume":"7","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ejmech.2019.06.016_bib67","doi-asserted-by":"crossref","first-page":"2688","DOI":"10.1038\/cddis.2017.18","article-title":"Hydrogen sulfide promotes autophagy of hepatocellular carcinoma cells through the PI3K\/Akt\/mTOR signaling pathway","volume":"8","author":"Wang","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ejmech.2019.06.016_bib68","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/ars.2011.4351","article-title":"Hydrogen sulfide: an endogenous mediator of resolution of inflammation and injury","volume":"17","author":"Wallace","year":"2012","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejmech.2019.06.016_bib69","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.3892\/or.2015.4248","article-title":"Exogenous hydrogen sulfide promotes C6 glioma cell growth through activation of the p38 MAPK\/ERK1\/2-COX-2 pathways","volume":"34","author":"Zhen","year":"2015","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.ejmech.2019.06.016_bib70","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1089\/ars.2013.5308","article-title":"Anti-cancer activity of new designer hydrogen sulfide-donating hybrids","volume":"20","author":"Kashfi","year":"2014","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejmech.2019.06.016_bib71","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.ejmech.2018.04.009","article-title":"Antiproliferative hydrogen sulfide releasing evodiamine derivatives and their apoptosis inducing properties","volume":"151","author":"Hu","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib72","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.ejmech.2017.06.012","article-title":"Syntheses, toxicities and anti-inflammation of H2S-donors based on non-steroidal anti-inflammatory drugs","volume":"138","author":"Li","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib73","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1161\/CIRCULATIONAHA.107.753467","article-title":"Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide","volume":"117","author":"Li","year":"2008","journal-title":"Circulation"},{"key":"10.1016\/j.ejmech.2019.06.016_bib74","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1021\/acs.orglett.7b04005","article-title":"Cyclic acyl disulfides and acyl selenylsulfides as the precursors for persulfides (RSSH), selenylsulfides (RSeSH), and hydrogen sulfide (H2S)","volume":"20","author":"Kang","year":"2018","journal-title":"Org. Lett."},{"key":"10.1016\/j.ejmech.2019.06.016_bib75","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1111\/j.1476-5381.2009.00611.x","article-title":"Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346)","volume":"159","author":"Wallace","year":"2010","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.ejmech.2019.06.016_bib76","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.bbrc.2012.02.051","article-title":"NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in\u00a0vitro and in a xenograft mouse model","volume":"419","author":"Chattopadhyay","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejmech.2019.06.016_bib77","doi-asserted-by":"crossref","first-page":"15560","DOI":"10.1073\/pnas.0705891104","article-title":"Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function","volume":"104","author":"Elrod","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/j.ejmech.2019.06.016_bib78","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.niox.2014.04.008","article-title":"AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in\u00a0vitro","volume":"41","author":"Szczesny","year":"2014","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.ejmech.2019.06.016_bib79","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1016\/j.clinthera.2014.08.005","article-title":"Safety, tolerability and pharmacokinetics of trimebutine 3-thiocarbamoylbenzenesulfonate (GIC-1001) in a randomized phase I integrated design study: single and multiple ascending doses and effect of food in healthy volunteers","volume":"36","author":"Paquette","year":"2014","journal-title":"Clin. Ther."},{"key":"10.1016\/j.ejmech.2019.06.016_bib80","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.ejmech.2017.08.022","article-title":"Synthesis and evaluation of asymmetric curcuminoid analogs as potential anticancer agents that downregulate NF-kB activation and enhance the sensitivity of gastric cancer cell lines to irinotecan chemotherapy","volume":"139","author":"Qiu","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib81","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1159\/000471932","article-title":"Exogenous hydrogen sulfide ameliorates diabetes-associated cognitive decline by regulating the mitochondria-mediated apoptotic pathway and IL-23\/IL-17 expression in db\/db mice","volume":"41","author":"Ma","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib82","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bioorg.2018.10.002","article-title":"Hydrogen sulfide releasing enmein-type diterpenoid derivatives as apoptosis inducers through mitochondria-related pathways","volume":"82","author":"Xu","year":"2018","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib83","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ejmech.2018.10.004","article-title":"Synthesis, toxicities and bio-activities of manganese complexes with CO and H2S dual donors","volume":"159","author":"Bai","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib84","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.ejmech.2018.01.069","article-title":"Novel enmein-type diterpenoid hybrids coupled with nitrogen mustards: synthesis of promising candidates for anticancer therapeutics","volume":"146","author":"Gao","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2019.06.016_bib85","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ejmech.2018.02.088","article-title":"Novel hybrids of brefeldin A and nitrogen mustards with improved antiproliferative selectivity: design, synthesis and antitumor biological evaluation","volume":"150","author":"Han","year":"2018","journal-title":"Eur. J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419305355?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523419305355?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T21:21:13Z","timestamp":1778534473000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523419305355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9]]},"references-count":85,"alternative-id":["S0223523419305355"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.06.016","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2019,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hydrogen sulfide donating ent-kaurane and spirolactone-type 6,7-seco-ent-kaurane derivatives: Design, synthesis and antiproliferative properties","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2019.06.016","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Masson SAS. All rights reserved.","name":"copyright","label":"Copyright"}]}}