{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:08:19Z","timestamp":1783631299497,"version":"3.55.0"},"reference-count":46,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004912","name":"Sichuan University","doi-asserted-by":"publisher","award":["HXQMX0092"],"award-info":[{"award-number":["HXQMX0092"]}],"id":[{"id":"10.13039\/501100004912","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.bmcl.2026.130596","type":"journal-article","created":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T15:24:02Z","timestamp":1771773842000},"page":"130596","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Design, synthesis and anti-Parkinson's disease bioactivity evaluation of isoquinoline derivatives as potent IDO1\/TDO dual inhibitors"],"prefix":"10.1016","volume":"136","author":[{"given":"Zhongzhen","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runxin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bmcl.2026.130596_bb0005","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1002\/mds.29700","article-title":"Management of impulse control and related disorders in Parkinson\u2019s disease: an expert consensus","volume":"39","author":"Debove","year":"2024","journal-title":"Mov Disord"},{"key":"10.1016\/j.bmcl.2026.130596_bb0010","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/sctm.20-0302","article-title":"Synthetic mRNA-based differentiation method enables early detection of Parkinson\u2019s phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells","volume":"10","author":"Akiyama","year":"2021","journal-title":"Stem Cells Transl Med"},{"key":"10.1016\/j.bmcl.2026.130596_bb0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2024.116444","article-title":"\u0391-Synuclein regulates cyclin D1 to promote abnormal initiation of the cell cycle and induce apoptosis in dopamine neurons","volume":"173","author":"Jia","year":"2024","journal-title":"Biomed Pharmacother"},{"key":"10.1016\/j.bmcl.2026.130596_bb0020","doi-asserted-by":"crossref","DOI":"10.1111\/jpi.13002","article-title":"Relationship between melatonin receptor agonists and Parkinson\u2019s disease","volume":"76","author":"Noguchi","year":"2024","journal-title":"J Pineal Res"},{"key":"10.1016\/j.bmcl.2026.130596_bb0025","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1002\/mds.26510","article-title":"Nonmotor features of Parkinson\u2019s disease subtypes","volume":"31","author":"Marras","year":"2016","journal-title":"Mov Disord"},{"key":"10.1016\/j.bmcl.2026.130596_bb0030","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1007\/s10072-016-2664-0","article-title":"Motor outcomes in patients with advanced Parkinson\u2019s disease treated with levodopa\/carbidopa intestinal gel in Italy: an interim analysis from the GREENFIELD observational study","volume":"37","author":"Lopiano","year":"2016","journal-title":"Neurol Sci"},{"key":"10.1016\/j.bmcl.2026.130596_bb0035","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1111\/cns.13140","article-title":"Mechanisms and roles of mitophagy in neurodegenerative diseases","volume":"25","author":"Wang","year":"2019","journal-title":"CNS Neurosci Ther"},{"key":"10.1016\/j.bmcl.2026.130596_bb0040","doi-asserted-by":"crossref","DOI":"10.1002\/smll.202408581","article-title":"The mitochondria-targeted micelle inhibits Alzheimer\u2019s disease progression by alleviating neuronal mitochondrial dysfunction and neuroinflammation","volume":"21","author":"Qian","year":"2025","journal-title":"Small"},{"key":"10.1016\/j.bmcl.2026.130596_bb0045","first-page":"1817","article-title":"Damage to dopaminergic neurons by oxidative stress in Parkinson\u2019s disease (review)","volume":"41","author":"Guo","year":"2018","journal-title":"Int J Mol Med"},{"key":"10.1016\/j.bmcl.2026.130596_bb0050","doi-asserted-by":"crossref","DOI":"10.1111\/acel.13031","article-title":"Oxidative stress in the aging substantia nigra and the etiology of Parkinson\u2019s disease","volume":"18","author":"Trist","year":"2019","journal-title":"Aging Cell"},{"key":"10.1016\/j.bmcl.2026.130596_bb0055","doi-asserted-by":"crossref","DOI":"10.1155\/2021\/9999146","article-title":"Neuroinflammation: an integrating overview of reactive-neuroimmune cell interactions in health and disease","volume":"2021","author":"K\u00f6lliker-Frers","year":"2021","journal-title":"Mediat Inflamm"},{"key":"10.1016\/j.bmcl.2026.130596_bb0060","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.3390\/cells11182908","article-title":"Neuroinflammation and Parkinson\u2019s disease-from neurodegeneration to therapeutic opportunities","volume":"11","author":"Ara\u00fajo","year":"2022","journal-title":"Cells"},{"key":"10.1016\/j.bmcl.2026.130596_bb0065","doi-asserted-by":"crossref","DOI":"10.1111\/ene.16499","article-title":"Understanding Parkinson disease in Spain: genetic and clinical insights","volume":"32","author":"G\u00f3mez-Garre","year":"2025","journal-title":"Eur J Neurol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0070","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40035-019-0165-9","article-title":"The interplay of aging, genetics and environmental factors in the pathogenesis of Parkinson\u2019s disease","volume":"8","author":"Pang","year":"2019","journal-title":"Transl Neurodegener"},{"key":"10.1016\/j.bmcl.2026.130596_bb0075","doi-asserted-by":"crossref","DOI":"10.1177\/1178646917691938","article-title":"Kynurenine pathway of tryptophan metabolism: regulatory and functional aspects","volume":"10","author":"Badawy","year":"2017","journal-title":"Int J Tryptophan Res"},{"key":"10.1016\/j.bmcl.2026.130596_bb0080","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.pnpbp.2017.04.035","article-title":"IDO chronic immune activation and tryptophan metabolic pathway: a potential pathophysiological link between depression and obesity","volume":"80","author":"Chaves Filho","year":"2018","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130596_bb0085","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00726-022-03161-5","article-title":"Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease","volume":"54","author":"Paeslack","year":"2022","journal-title":"Amino Acids"},{"key":"10.1016\/j.bmcl.2026.130596_bb0090","doi-asserted-by":"crossref","DOI":"10.1126\/science.aaf9794","article-title":"Kynurenines: tryptophan\u2019s metabolites in exercise, inflammation, and mental health","volume":"357","author":"Cervenka","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.bmcl.2026.130596_bb0095","doi-asserted-by":"crossref","DOI":"10.1016\/j.phymed.2023.154852","article-title":"Pulsatilla chinensis saponins ameliorated murine depression by inhibiting intestinal inflammation mediated IDO1 overexpression and rebalancing tryptophan metabolism","volume":"116","author":"Wang","year":"2023","journal-title":"Phytomedicine"},{"key":"10.1016\/j.bmcl.2026.130596_bb0100","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/cmi.2017.143","article-title":"IDO1 in cancer: a Gemini of immune checkpoints","volume":"15","author":"Zhai","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0105","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23116300","article-title":"An emerging cross-species marker for organismal health: tryptophan-kynurenine pathway","volume":"23","author":"Jamshed","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.bmcl.2026.130596_bb0110","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-021-02175-2","article-title":"Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease","volume":"18","author":"Chen","year":"2021","journal-title":"J Neuroinflammation"},{"key":"10.1016\/j.bmcl.2026.130596_bb0115","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.3390\/ijms20061482","article-title":"Glutamatergic signaling along the microbiota-gut-brain axis","volume":"20","author":"Baj","year":"2019","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.bmcl.2026.130596_bb0120","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neuroscience.2008.11.055","article-title":"Specific inhibition of kynurenate synthesis enhances extracellular dopamine levels in the rodent striatum","volume":"159","author":"Amori","year":"2009","journal-title":"Neuroscience"},{"key":"10.1016\/j.bmcl.2026.130596_bb0125","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.biopsych.2018.09.031","article-title":"The impact of stress and major depressive disorder on hippocampal and medial prefrontal cortex morphology","volume":"85","author":"Belleau","year":"2019","journal-title":"Biol Psychiatry"},{"key":"10.1016\/j.bmcl.2026.130596_bb0130","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrn3257","article-title":"Kynurenines in the mammalian brain: when physiology meets pathology","volume":"13","author":"Schwarcz","year":"2012","journal-title":"Nat Rev Neurosci"},{"key":"10.1016\/j.bmcl.2026.130596_bb0135","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.00151","article-title":"The role of indoleamine-2,3-dioxygenase in cancer development, diagnostics, and therapy","volume":"9","author":"Horny\u00e1k","year":"2018","journal-title":"Front Immunol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0140","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/arch.20159","article-title":"Biochemical mechanisms leading to tryptophan 2,3-dioxygenase activation","volume":"64","author":"Li","year":"2007","journal-title":"Arch Insect Biochem Physiol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0145","doi-asserted-by":"crossref","first-page":"2771","DOI":"10.7150\/jca.31727","article-title":"Role of IDO and TDO in cancers and related diseases and the therapeutic implications","volume":"10","author":"Ye","year":"2019","journal-title":"J Cancer"},{"key":"10.1016\/j.bmcl.2026.130596_bb0150","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1002\/ijc.31417","article-title":"1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells","volume":"143","author":"Liu","year":"2018","journal-title":"Int J Cancer"},{"key":"10.1016\/j.bmcl.2026.130596_bb0155","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.it.2012.10.001","article-title":"Indoleamine 2,3 dioxygenase and metabolic control of immune responses","volume":"34","author":"Munn","year":"2013","journal-title":"Trends Immunol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0160","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.nbd.2003.12.015","article-title":"Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia","volume":"15","author":"Miller","year":"2004","journal-title":"Neurobiol Dis"},{"key":"10.1016\/j.bmcl.2026.130596_bb0165","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-4615-0135-0_12","article-title":"Expression of the kynurenine pathway enzymes in human microglia and macrophages","volume":"527","author":"Guillemin","year":"2003","journal-title":"Adv Exp Med Biol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0170","doi-asserted-by":"crossref","first-page":"9161","DOI":"10.1021\/acs.jmedchem.9b01079","article-title":"N-benzyl\/aryl substituted tryptanthrin as dual inhibitors of indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase","volume":"62","author":"Yang","year":"2019","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130596_bb0175","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1021\/acsmedchemlett.0c00004","article-title":"Implementation of the CYP index for the design of selective tryptophan-2,3-dioxygenase inhibitors","volume":"11","author":"Parr","year":"2020","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2026.130596_bb0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2019.111985","article-title":"Design, synthesis and biological evaluation of indole-2-carboxylic acid derivatives as IDO1\/TDO dual inhibitors","volume":"188","author":"Cui","year":"2020","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130596_bb0185","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1080\/13543776.2019.1556638","article-title":"Current state on tryptophan 2,3-dioxygenase inhibitors: a patent review","volume":"29","author":"Kozlova","year":"2019","journal-title":"Expert Opin Ther Pat"},{"key":"10.1016\/j.bmcl.2026.130596_bb0190","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1073\/pnas.1113873109","article-title":"Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase","volume":"109","author":"Pilotte","year":"2012","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmcl.2026.130596_bb0195","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1080\/13543776.2016.1189531","article-title":"Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015)","volume":"26","author":"Z\u00e1dori","year":"2016","journal-title":"Expert Opin Ther Pat"},{"key":"10.1016\/j.bmcl.2026.130596_bb0200","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nrd3793","article-title":"Kynurenines in the CNS: recent advances and new questions","volume":"12","author":"V\u00e9csei","year":"2013","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.bmcl.2026.130596_bb0205","doi-asserted-by":"crossref","first-page":"8303","DOI":"10.1021\/acs.jmedchem.1c00303","article-title":"X-ray structure-guided discovery of a potent, orally bioavailable, dual human indoleamine\/tryptophan 2,3-dioxygenase (hIDO\/hTDO) inhibitor that shows activity in a mouse model of Parkinson\u2019s disease","volume":"64","author":"Ning","year":"2021","journal-title":"J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130596_bb0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116852","article-title":"Discovery, synthesis and biological evaluation of novel isoquinoline derivatives as potent indoleamine 2, 3-dioxygenase 1 and tryptophan 2, 3-dioxygenase dual inhibitors","volume":"279","author":"Lin","year":"2024","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130596_bb0215","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1002\/prot.24653","article-title":"Structural and functional analyses of human tryptophan 2,3-dioxygenase","volume":"82","author":"Meng","year":"2014","journal-title":"Proteins"},{"key":"10.1016\/j.bmcl.2026.130596_bb0220","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.ejmech.2017.11.088","article-title":"Recent discovery of indoleamine-2,3-dioxygenase 1 inhibitors targeting cancer immunotherapy","volume":"143","author":"Weng","year":"2018","journal-title":"Eur J Med Chem"},{"key":"10.1016\/j.bmcl.2026.130596_bb0225","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2025.1632446","article-title":"IDO and TDO inhibitors in cancer immunotherapy: mechanisms, clinical development, and future directions","volume":"16","author":"Al-Zoubi","year":"2025","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.bmcl.2026.130596_bb0230","doi-asserted-by":"crossref","first-page":"11214","DOI":"10.1021\/acs.jmedchem.2c00677","article-title":"Discovery of 1-(hetero)aryl-\u03b2-carboline derivatives as IDO1\/TDO dual inhibitors with antidepressant activity","volume":"65","author":"Zhang","year":"2022","journal-title":"J Med Chem"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26000636?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X26000636?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T01:54:54Z","timestamp":1777600494000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X26000636"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":46,"alternative-id":["S0960894X26000636"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130596","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and anti-Parkinson's disease bioactivity evaluation of isoquinoline derivatives as potent IDO1\/TDO dual inhibitors","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2026.130596","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"130596"}}