{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:40:54Z","timestamp":1792644054613,"version":"4.5.0"},"reference-count":88,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100022955","name":"Fundamental Research Funds for the Provincial Universities of Zhejiang","doi-asserted-by":"publisher","award":["RF-A2024014"],"award-info":[{"award-number":["RF-A2024014"]}],"id":[{"id":"10.13039\/100022955","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2412100"],"award-info":[{"award-number":["W2412100"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2804202"],"award-info":[{"award-number":["2022YFC2804202"]}],"id":[{"id":"10.13039\/501100012166","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":[[2026,12]]},"DOI":"10.1016\/j.ejmech.2026.119321","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:44:47Z","timestamp":1789515887000},"page":"119321","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Directed scaffold evolution of chrysin for the development of potent carboxylesterase 2 inhibitors"],"prefix":"10.1016","volume":"320","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3682-2674","authenticated-orcid":false,"given":"Xiaoze","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangwei","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7405-5773","authenticated-orcid":false,"given":"Tianyi","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guishun","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhikun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Nuo","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Wei","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4479-4626","authenticated-orcid":false,"given":"Damien","family":"Bonne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib1a","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. Nat. Prod."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib1b","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1021\/acs.jnatprod.9b01285","article-title":"Natural Products as Sources of New Drugs over the Nearly Four Decades from 01\/1981 to 09\/2019","volume":"83","author":"Newman","year":"2020","journal-title":"J. Nat. Prod."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib2a","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1038\/s41467-018-03546-9","article-title":"Scalable synthesis enabling multilevel bio-evaluations of natural products for discovery of lead compounds","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat. Commun."},{"issue":"7","key":"10.1016\/j.ejmech.2026.119321_bib2b","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.tibtech.2020.03.013","article-title":"Genetic Biosensor Design for Natural Product Biosynthesis in Microorganisms","volume":"38","author":"Hossain","year":"2020","journal-title":"Trends Biotechnol."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib2c","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural products in drug discovery: advances and opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"issue":"7211","key":"10.1016\/j.ejmech.2026.119321_bib3a","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature07370","article-title":"Natural products as inspiration for the development of asymmetric catalysis","volume":"455","author":"Mohr","year":"2008","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib3b","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1021\/ar5004303","article-title":"Intramolecular Dearomative Oxidative Coupling of Indoles: A Unified Strategy for the Total Synthesis of Indoline Alkaloids","volume":"48","author":"Zi","year":"2015","journal-title":"Acc. Chem. Res."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib4a","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1038\/ncomms7516","article-title":"De novo branching cascades for structural and functional diversity in small molecules","volume":"6","author":"Garcia-Castro","year":"2015","journal-title":"Nat. Commun."},{"issue":"22","key":"10.1016\/j.ejmech.2026.119321_bib4b","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1073\/pnas.1614680114","article-title":"Retrospective analysis of natural products provides insights for future discovery trends","volume":"114","author":"Pye","year":"2017","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41557-019-0411-x","article-title":"Principle and design of pseudo-natural products","volume":"12","author":"Karageorgis","year":"2020","journal-title":"Nat. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119321_bib6","doi-asserted-by":"crossref","DOI":"10.1002\/minf.202000057","article-title":"Privileged scaffold analysis of natural products with deep learning-based indication prediction model","volume":"39","author":"Lai","year":"2020","journal-title":"Mol. Inf."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib7a","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/ncomms1081","article-title":"Diversity-oriented synthesis as a tool for the discovery of novel biologically active small molecules","volume":"1","author":"Galloway","year":"2010","journal-title":"Nat. Commun."},{"issue":"42","key":"10.1016\/j.ejmech.2026.119321_bib7b","doi-asserted-by":"crossref","first-page":"14629","DOI":"10.1021\/ja508343a","article-title":"Privileged Structures: Efficient Chemical \u201cNavigators\u201d toward Unexplored Biologically Relevant Chemical Spaces","volume":"136","author":"Kim","year":"2014","journal-title":"J. Am. Chem. Soc."},{"issue":"6","key":"10.1016\/j.ejmech.2026.119321_bib8a","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1038\/s41557-019-0261-6","article-title":"Diverse compounds from pleuromutilin lead to a thioredoxin inhibitor and inducer of ferroptosis","volume":"11","author":"Llabani","year":"2019","journal-title":"Nat. Chem."},{"issue":"29","key":"10.1016\/j.ejmech.2026.119321_bib8b","doi-asserted-by":"crossref","first-page":"16119","DOI":"10.1002\/anie.202104228","article-title":"Limonin as a Starting Point for the Construction of Compounds with High Scaffold Diversity","volume":"60","author":"Furiassi","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"issue":"41","key":"10.1016\/j.ejmech.2026.119321_bib9","doi-asserted-by":"crossref","first-page":"14715","DOI":"10.1002\/anie.201907853","article-title":"Design, synthesis, and phenotypic profiling of pyrano-furo-pyridone pseudo natural products","volume":"58","author":"Christoforow","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119321_bib10","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1039\/D0NP00015A","article-title":"Guided by evolution: from biology oriented synthesis to pseudo natural products","volume":"37","author":"Cremosnik","year":"2020","journal-title":"Nat. Prod. Rep."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib11a","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1021\/ar700155p","article-title":"Function-Oriented Synthesis, Step Economy, and Drug Design","volume":"41","author":"Wender","year":"2008","journal-title":"Acc. Chem. Res."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119321_bib11b","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1039\/D0NP00048E","article-title":"Bridging the gap between natural product synthesis and drug discovery","volume":"37","author":"Truax","year":"2020","journal-title":"Nat. Prod. Rep."},{"key":"10.1016\/j.ejmech.2026.119321_bib11c","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.115030","article-title":"Function-oriented synthesis of Imidazo[1,2-a]pyrazine and Imidazo[1,2-b]pyridazine derivatives as potent PI3K\/mTOR dual inhibitors","volume":"247","author":"Li","year":"2023","journal-title":"Eur. J. Med. Chem."},{"issue":"9","key":"10.1016\/j.ejmech.2026.119321_bib12a","doi-asserted-by":"crossref","first-page":"4648","DOI":"10.1002\/anie.202013731","article-title":"Design, Synthesis, and Biological Evaluation of Chemically and Biologically Diverse Pyrroquinoline Pseudo Natural Products","volume":"60","author":"Liu","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"issue":"29","key":"10.1016\/j.ejmech.2026.119321_bib12b","doi-asserted-by":"crossref","first-page":"7936","DOI":"10.1039\/D3SC01240A","article-title":"A highly enantioselective intramolecular 1,3-dipolar cycloaddition yields novel pseudo-natural product inhibitors of the Hedgehog signalling pathway","volume":"14","author":"Liu","year":"2023","journal-title":"Chem. Sci."},{"key":"10.1016\/j.ejmech.2026.119321_bib12c","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/s41557-024-01458-4","article-title":"A divergent intermediate strategy yields biologically diverse pseudo-natural products","volume":"16","author":"Bag","year":"2024","journal-title":"Nat. Chem."},{"key":"10.1016\/j.ejmech.2026.119321_bib13a","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jhazmat.2014.10.033","article-title":"Enantioselective bioactivity, acute toxicity and dissipation in vegetables of the chiral triazole fungicide flutriafol","volume":"284","author":"Zhang","year":"2015","journal-title":"J. Hazard. Mater"},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib13b","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-79251-9","article-title":"Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist","volume":"10","author":"Mays","year":"2020","journal-title":"Sci. Rep."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119321_bib13c","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1021\/acs.orglett.8b01316","article-title":"Asymmetric Construction of a Multi-Pharmacophore-Containing Dispirotriheterocyclic Scaffold and Identification of a Human Carboxylesterase 1 Inhibitor","volume":"20","author":"Bao","year":"2018","journal-title":"Org. Lett."},{"issue":"10","key":"10.1016\/j.ejmech.2026.119321_bib14a","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/s43588-024-00699-0","article-title":"The future of machine learning for small-molecule drug discovery will be driven by data","volume":"4","author":"Durant","year":"2024","journal-title":"Nat. Comput. Sci."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib14b","doi-asserted-by":"crossref","first-page":"4993","DOI":"10.1038\/s41467-024-49388-6","article-title":"t-SMILES: a fragment-based molecular representation framework for de novo ligand design","volume":"15","author":"Wu","year":"2024","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib14c","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41591-024-03434-4","article-title":"Artificial intelligence in drug development","volume":"31","author":"Zhang","year":"2025","journal-title":"Nat. Med."},{"issue":"15","key":"10.1016\/j.ejmech.2026.119321_bib15a","doi-asserted-by":"crossref","first-page":"7887","DOI":"10.1021\/acs.jcim.5c00456","article-title":"Expert-Guided Substructure Information Bottleneck for Molecular Property Prediction","volume":"65","author":"Jiang","year":"2025","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.119321_bib15b","doi-asserted-by":"crossref","DOI":"10.1016\/j.ins.2025.122357","article-title":"Knowledge-enhanced Relation Graph and Task Sampling for few-shot molecular property prediction","volume":"718","author":"Wang","year":"2025","journal-title":"Inf. Sci."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib15c","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbae165","article-title":"Mix-Key: graph mixup with key structures for molecular property prediction","volume":"25","author":"Jiang","year":"2024","journal-title":"Briefings Bioinf."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib15d","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1109\/TCBBIO.2025.3553815","article-title":"Molecular Connectivity Index-Based Data Augmentation for Molecular Property Prediction","volume":"22","author":"Wang","year":"2025","journal-title":"IEEE Transactions on Computational Biology and Bioinformatics"},{"issue":"5","key":"10.1016\/j.ejmech.2026.119321_bib16a","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.apsb.2018.05.005","article-title":"Human carboxylesterases: a comprehensive review","volume":"8","author":"Wang","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"10.1016\/j.ejmech.2026.119321_bib16b","doi-asserted-by":"crossref","DOI":"10.1016\/j.trac.2022.116620","article-title":"High-throughput optical assays for sensing serine hydrolases in living systems and their applications","volume":"152","author":"Jin","year":"2022","journal-title":"TrAC, Trends Anal. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib16c","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1021\/acs.jmedchem.3c01850","article-title":"Tight-Binding Small-Molecule Carboxylesterase 2 Inhibitors Reduce Intracellular Irinotecan Activation","volume":"67","author":"Kailass","year":"2024","journal-title":"J. Med. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.phrs.2011.11.007","article-title":"Loperamide, an antidiarrhea drug, has antitumor activity by inducing cell apoptosis","volume":"65","author":"Gong","year":"2012","journal-title":"Pharmacol. Res."},{"issue":"SUPPL. 3","key":"10.1016\/j.ejmech.2026.119321_bib18a","first-page":"S11","article-title":"Loperamide: A pharmacological review","volume":"7","author":"Baker","year":"2007","journal-title":"Rev. Gastroenterol. Disord."},{"key":"10.1016\/j.ejmech.2026.119321_bib18b","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2023.117637","article-title":"The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism","volume":"322","author":"Qin","year":"2024","journal-title":"J. Ethnopharmacol."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib19a","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1124\/jpet.112.201640","article-title":"Carboxylesterase 1 as a Determinant of Clopidogrel Metabolism and Activation","volume":"344","author":"Zhu","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"5","key":"10.1016\/j.ejmech.2026.119321_bib19b","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3390\/md16050153","article-title":"Determination of the \u03bc-Conotoxin PIIIA Specificity Against Voltage-Gated Sodium Channels from Binding Energy Calculations","volume":"16","author":"Chen","year":"2018","journal-title":"Mar. Drugs"},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib19c","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.celrep.2016.12.070","article-title":"Human Carboxylesterase 2 Reverses Obesity-Induced Diacylglycerol Accumulation and Glucose Intolerance","volume":"18","author":"Ruby","year":"2017","journal-title":"Cell Rep."},{"issue":"2","key":"10.1016\/j.ejmech.2026.119321_bib19d","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1007\/s13238-017-0437-z","article-title":"Carboxylesterases in lipid metabolism: from mouse to human","volume":"9","author":"Lian","year":"2017","journal-title":"Protein Cell"},{"key":"10.1016\/j.ejmech.2026.119321_bib20a","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.fitote.2015.01.004","article-title":"Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxylesterase 2","volume":"101","author":"Li","year":"2015","journal-title":"Fitoterapia"},{"key":"10.1016\/j.ejmech.2026.119321_bib20b","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.fitote.2017.01.010","article-title":"Recent progress in the discovery of natural inhibitors against human carboxylesterases","volume":"117","author":"Wang","year":"2017","journal-title":"Fitoterapia"},{"issue":"29","key":"10.1016\/j.ejmech.2026.119321_bib20c","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1002\/ejoc.201402043","article-title":"Recent Developments in the Chemistry of gem-Halonitro Compounds","volume":"2014","author":"Soengas","year":"2014","journal-title":"Eur. J. Org. Chem."},{"issue":"15","key":"10.1016\/j.ejmech.2026.119321_bib20d","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2020.115565","article-title":"Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi","volume":"28","author":"Wood","year":"2020","journal-title":"Bioorg. Med. Chem."},{"issue":"15","key":"10.1016\/j.ejmech.2026.119321_bib20e","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1039\/D1OB00146A","article-title":"Copper-catalyzed [3 + 2]-cycloaddition of \u03b1-halonitroalkenes with azomethine ylides: facile synthesis of multisubstituted pyrrolidines and pyrroles","volume":"19","author":"Motornov","year":"2021","journal-title":"Org. Biomol. Chem."},{"issue":"44","key":"10.1016\/j.ejmech.2026.119321_bib20f","doi-asserted-by":"crossref","first-page":"8725","DOI":"10.1039\/D2OB01571D","article-title":"Organocatalytic enantioselective synthesis of dihydronaphthofurans and dihydrobenzofurans: reaction development and insights into stereoselectivity","volume":"20","author":"Susam","year":"2022","journal-title":"Org. Biomol. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2026.119321_bib20g","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1055\/s-0042-1751360","article-title":"Organo-photocatalytic Synthesis of Functionalized Pyrroles from 2H-Azirines and \u03b1-Substituted Nitroalkenes","volume":"6","author":"Devi","year":"2022","journal-title":"SynOpen"},{"issue":"22","key":"10.1016\/j.ejmech.2026.119321_bib20h","doi-asserted-by":"crossref","DOI":"10.1002\/ejoc.202300218","article-title":"Basicity-Controlled [3+2] Cyclization of 3-Hydroxyquinolin-ones and \u03b2-Chlorinated Nitrostyrenes","volume":"26","author":"Wu","year":"2023","journal-title":"Eur. J. Org. Chem."},{"key":"10.1016\/j.ejmech.2026.119321_bib21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.fitote.2016.09.022","article-title":"Identification and characterization of naturally occurring inhibitors against human carboxylesterase 2 in white mulberry Root-bark","volume":"115","author":"Liu","year":"2016","journal-title":"Fitoterapia"},{"issue":"6","key":"10.1016\/j.ejmech.2026.119321_bib22","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3109\/00498254.2015.1091521","article-title":"Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1)","volume":"46","author":"Sun","year":"2016","journal-title":"Xenobiotica"},{"issue":"5","key":"10.1016\/j.ejmech.2026.119321_bib23","doi-asserted-by":"crossref","first-page":"2188","DOI":"10.3390\/ijms11052188","article-title":"Apoptotic effects of chrysin in human cancer cell lines","volume":"11","author":"Khoo","year":"2010","journal-title":"Int. J. Mol. Sci."},{"issue":"10","key":"10.1016\/j.ejmech.2026.119321_bib24a","doi-asserted-by":"crossref","first-page":"5274","DOI":"10.1021\/acs.joc.7b00578","article-title":"Radical Nitration-Debromination of \u03b1-Bromo-\u03b1-fluoroalkenes as a Stereoselective Route to Aromatic \u03b1-Fluoronitroalkenes\u2014Functionalized Fluorinated Building Blocks for Organic Synthesis","volume":"82","author":"Motornov","year":"2017","journal-title":"J. Org. Chem."},{"issue":"9","key":"10.1016\/j.ejmech.2026.119321_bib24b","doi-asserted-by":"crossref","first-page":"5997","DOI":"10.1021\/acs.joc.3c00335","article-title":"Rapid Assembly of Spiroisoxazolidines by [4 + 1] Dearomative Spiroannulation of \u03b1-Bromo-\u03b2-naphthol and Nitroolefin","volume":"88","author":"Qi","year":"2023","journal-title":"J. Org. Chem."},{"issue":"14","key":"10.1016\/j.ejmech.2026.119321_bib24c","doi-asserted-by":"crossref","first-page":"10122","DOI":"10.1021\/acs.joc.3c00935","article-title":"Barton\u2013Zard Reaction of \u03b2-Fluoro-\u03b2-nitrostyrenes\u2500a Selective Route to Functionalized 4-Fluoropyrroles","volume":"88","author":"Larkovich","year":"2023","journal-title":"J. Org. Chem."},{"issue":"19","key":"10.1016\/j.ejmech.2026.119321_bib24d","doi-asserted-by":"crossref","first-page":"3260","DOI":"10.1002\/adsc.202300625","article-title":"Traceless Directing Group Enabled One-Pot Regiospecific Synthesis of 2,3-Diaryl-4-Fluoropyrroles","volume":"365","author":"Wang","year":"2023","journal-title":"Adv. Synth. Catal."},{"key":"10.1016\/j.ejmech.2026.119321_bib25","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.phytochem.2017.09.016","article-title":"Chrysin: sources, beneficial pharmacological activities, and molecular mechanism of action","volume":"145","author":"Mani","year":"2018","journal-title":"Phytochemistry"},{"issue":"22","key":"10.1016\/j.ejmech.2026.119321_bib26a","doi-asserted-by":"crossref","first-page":"6525","DOI":"10.1002\/anie.201601660","article-title":"Quinine-Catalyzed Asymmetric Synthesis of 2,2\u2032-Binaphthol-Type Biaryls under Mild Reaction Conditions","volume":"55","author":"Moliterno","year":"2016","journal-title":"Angew. Chem. Int. Ed."},{"issue":"1","key":"10.1016\/j.ejmech.2026.119321_bib26b","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/anie.201608150","article-title":"Design and Enantioselective Construction of Axially Chiral Naphthyl-Indole Skeletons","volume":"56","author":"Zhang","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"issue":"24","key":"10.1016\/j.ejmech.2026.119321_bib26c","doi-asserted-by":"crossref","first-page":"6276","DOI":"10.1021\/acs.orglett.6b03073","article-title":"Exploring the Reactivity of Nitro-Activated 1,3-Enynes in an Organocatalytic One-Pot, Three-Component Coupling Reaction: A Tandem Catalytic Approach to a Novel 3-Nitrochroman Scaffold","volume":"18","author":"Xiao","year":"2016","journal-title":"Org. Lett."},{"issue":"23","key":"10.1016\/j.ejmech.2026.119321_bib26d","doi-asserted-by":"crossref","first-page":"6392","DOI":"10.1021\/acs.orglett.7b03250","article-title":"Phosphine-Catalyzed Asymmetric (3+2) Annulations of \u03b4-Acetoxy Allenoates with 2-Naphthols","volume":"19","author":"Wang","year":"2017","journal-title":"Org. Lett."},{"issue":"21","key":"10.1016\/j.ejmech.2026.119321_bib26e","doi-asserted-by":"crossref","first-page":"5532","DOI":"10.1002\/anie.201300231","article-title":"Acid-Catalyzed In Situ Generation of Less Accessible or Unprecedented N-Boc Imines from N-Boc Aminals","volume":"52","author":"Kano","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"issue":"37","key":"10.1016\/j.ejmech.2026.119321_bib26f","article-title":"Asymmetric (4+n) Cycloadditions of Indolyldimethanols for the Synthesis of Enantioenriched Indole-Fused Rings","volume":"62","author":"Zhang","year":"2023","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.ejmech.2026.119321_bib27","unstructured":"https:\/\/www.ebi.ac.uk\/chembl\/."},{"key":"10.1016\/j.ejmech.2026.119321_bib28","unstructured":"Wang Z, Jiang T, Wang J, Xuan Q. Multi-modal representation learning for molecular property prediction: sequence, graph, geometry. arXiv - QuanBio - Molecular Networks 2024:2401.03369."},{"issue":"5","key":"10.1016\/j.ejmech.2026.119321_bib29a","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1021\/jm991128y","article-title":"C-Isoprenylation of Flavonoids Enhances Binding Affinity toward P-Glycoprotein and Modulation of Cancer Cell Chemoresistance","volume":"44","author":"Comte","year":"2001","journal-title":"J. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2026.119321_bib29b","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1021\/jm040770b","article-title":"Effects of Flavonoids on Cell Proliferation and Caspase Activation in a Human Colonic Cell Line HT29: An SAR Study","volume":"48","author":"Daskiewicz","year":"2005","journal-title":"J. Med. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2026.119321_bib29c","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1021\/ja808402e","article-title":"Total Synthesis of the Potent Anticancer Aglaia Metabolites (\u2212)-Silvestrol and (\u2212)-Episilvestrol and the Active Analogue (\u2212)-4\u2032-Desmethoxyepisilvestrol","volume":"131","author":"Adams","year":"2009","journal-title":"J. Am. Chem. Soc."},{"issue":"16","key":"10.1016\/j.ejmech.2026.119321_bib29d","doi-asserted-by":"crossref","first-page":"6481","DOI":"10.1021\/acs.jmedchem.5b00494","article-title":"A Ligand-Based Drug Design. Discovery of 4-Trifluoromethyl-7,8-pyranocoumarin as a Selective Inhibitor of Human Cytochrome P450 1A2","volume":"58","author":"Liu","year":"2015","journal-title":"J. Med. Chem."},{"issue":"13","key":"10.1016\/j.ejmech.2026.119321_bib29e","doi-asserted-by":"crossref","first-page":"2948","DOI":"10.1016\/j.bmc.2019.05.028","article-title":"2-Phenyl-8-(1-phenylallyl)-chromenone compounds have a pan-PPAR modulator pharmacophore","volume":"27","author":"Ahn","year":"2019","journal-title":"Bioorg. Med. Chem."},{"issue":"9","key":"10.1016\/j.ejmech.2026.119321_bib29f","doi-asserted-by":"crossref","DOI":"10.1002\/asia.202200120","article-title":"1, 2-trans-Stereoselective 7-O-Glycosylation of Flavonoids with Unprotected Pyranoses by Mitsunobu Reaction","volume":"17","author":"Shi","year":"2022","journal-title":"Chem. Asian J."},{"key":"10.1016\/j.ejmech.2026.119321_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2019.103199","article-title":"Biflavones from Ginkgo biloba as inhibitors of human thrombin","volume":"92","author":"Chen","year":"2019","journal-title":"Bioorg. Chem."},{"issue":"24","key":"10.1016\/j.ejmech.2026.119321_bib31","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.1039\/D1AY00415H","article-title":"A high-throughput screening assay for dipeptidyl peptidase-IV inhibitors using human plasma","volume":"13","author":"Zhang","year":"2021","journal-title":"Anal. Methods"},{"key":"10.1016\/j.ejmech.2026.119321_bib32","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112856","article-title":"Design, synthesis and biological evaluation of indanone\u2013chalcone hybrids as potent and selective hCES2A inhibitors","volume":"209","author":"Huo","year":"2021","journal-title":"Eur. J. Med. Chem."},{"issue":"42","key":"10.1016\/j.ejmech.2026.119321_bib33a","doi-asserted-by":"crossref","first-page":"26245","DOI":"10.1073\/pnas.2010264117","article-title":"Cryo-EM structures reveal distinct mechanisms of inhibition of the human multidrug transporter ABCB1","volume":"117","author":"Nosol","year":"2020","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"5","key":"10.1016\/j.ejmech.2026.119321_bib33b","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1002\/ps.6250","article-title":"Design, synthesis and mode of action of novel 3-chloro-6-pyrazolyl picolinate derivatives as herbicide candidates","volume":"77","author":"Yang","year":"2021","journal-title":"Pest. Manage. Sci."},{"issue":"2","key":"10.1016\/j.ejmech.2026.119321_bib33c","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/cmdc.202000581","article-title":"Synthesis and Structure-Activity Relationships of 3-Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors","volume":"16","author":"Zhao","year":"2021","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2026.119321_bib34","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmc.2021.116187","article-title":"Discovery of pyrazolones as novel carboxylesterase 2 inhibitors that potently inhibit the adipogenesis in cells","volume":"40","author":"Qian","year":"2021","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.119321_bib35","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ijbiomac.2019.02.074","article-title":"Evaluation of structural, functional, and anti-oxidant potential of differentially extracted polysaccharides from potatoes peels","volume":"129","author":"Xu","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"issue":"6","key":"10.1016\/j.ejmech.2026.119321_bib36","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.1021\/jacs.6b11079","article-title":"Enantioselective syntheses of furan atropisomers by an oxidative central-to-axial chirality conversion strategy","volume":"139","author":"Raut","year":"2017","journal-title":"J. Am. Chem. Soc."},{"issue":"13","key":"10.1016\/j.ejmech.2026.119321_bib37a","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1039\/C8QO00305J","article-title":"Organocatalytic asymmetric [3 + 2] annulation of 1,4-dithiane-2,5-diol with azlactones: access to chiral dihydrothiophen-2(3H)-one derivatives","volume":"5","author":"Yu","year":"2018","journal-title":"Org. Chem. Front."},{"issue":"115","key":"10.1016\/j.ejmech.2026.119321_bib37b","doi-asserted-by":"crossref","first-page":"95079","DOI":"10.1039\/C5RA19593D","article-title":"Mechanistic investigations of a bifunctional squaramide organocatalyst in asymmetric Michael reaction and observation of stereoselective retro-Michael reaction","volume":"5","author":"Varga","year":"2015","journal-title":"RSC Adv."},{"issue":"11","key":"10.1016\/j.ejmech.2026.119321_bib38a","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1124\/dmd.107.015727","article-title":"Specificity of Procaine and Ester Hydrolysis by Human, Minipig, and Rat Skin and Liver","volume":"35","author":"Jewell","year":"2007","journal-title":"Drug Metab. Dispos."},{"issue":"8","key":"10.1016\/j.ejmech.2026.119321_bib38b","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1124\/dmd.111.039628","article-title":"Characterization of Recombinant Human Carboxylesterases: Fluorescein Diacetate as a Probe Substrate for Human Carboxylesterase 2","volume":"39","author":"Wang","year":"2011","journal-title":"Drug Metab. Dispos."},{"key":"10.1016\/j.ejmech.2026.119321_bib39","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.bioorg.2018.01.011","article-title":"Characterization and structure-activity relationship studies of flavonoids as inhibitors against human carboxylesterase 2","volume":"77","author":"Weng","year":"2018","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.119321_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.snb.2021.130033","article-title":"Rational design and development of a novel and highly specific near-infrared fluorogenic substrate for sensing and imaging of human pancreatic lipase in living systems","volume":"341","author":"Hu","year":"2021","journal-title":"Sens. Actuators, B"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600766X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600766X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:21:06Z","timestamp":1792642866000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342600766X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":88,"alternative-id":["S022352342600766X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119321","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Directed scaffold evolution of chrysin for the development of potent carboxylesterase 2 inhibitors","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.119321","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"119321"}}