{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:07:21Z","timestamp":1787062041460,"version":"build-2736575974"},"reference-count":55,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The involvement of human carbonic anhydrase (hCA) IX\/XII in the pathogenesis and progression of many types of cancer is well acknowledged, and more recently human monoamine oxidases (hMAOs) A and B have been found important contributors to tumor development and aggressiveness. With a view of an enzymatic dual-blockade approach, in this investigation, new coumarin-based amino acyl and (pseudo)-dipeptidyl derivatives were synthesized and firstly evaluated in vitro for inhibitory activity and selectivity against membrane-bound and cytosolic hCAs (hCA IX\/XII over hCA I\/II), as well as the hMAOs, to estimate their potential as anticancer agents. De novo design of peptide-coumarin conjugates was subsequently carried out and involved the combination of the widely explored coumarin nucleus with the unique biophysical and structural properties of native or modified peptides. All compounds displayed nanomolar inhibitory activities towards membrane-anchored hCAs, whilst they were unable to block the ubiquitous CA I and II isoforms. Structural features pertinent to potent and selective CA inhibitory activity are discussed, and modeling studies were found to support the biological data. Lower potency inhibition of the hMAOs was observed, with most compounds showing preferential inhibition of hMAO-A. The binding of the most potent ligands (6 and 16) to the hydrophobic active site of hMAO-A was investigated in an attempt to explain selectivity on the molecular level. Calculated Ligand Efficiency values indicate that compound 6 has the potential to serve as a lead compound for developing innovative anticancer agents based on the dual inhibition strategy. This information may help design new coumarin-based peptide molecules with diverse bioactivities.<\/jats:p>","DOI":"10.3390\/molecules27227884","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:36:36Z","timestamp":1668566196000},"page":"7884","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Coumarin-Based Dual Inhibitors of Human Carbonic Anhydrases and Monoamine Oxidases Featuring Amino Acyl and (Pseudo)-Dipeptidyl Appendages: In Vitro and Computational Studies"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5198-0051","authenticated-orcid":false,"given":"Mariangela","family":"Agamennone","sequence":"first","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2401-7547","authenticated-orcid":false,"given":"Marialuigia","family":"Fantacuzzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-9440","authenticated-orcid":false,"given":"Simone","family":"Carradori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u00e9l","family":"Petzer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7114-8120","authenticated-orcid":false,"given":"Jacobus P.","family":"Petzer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Chemistry, School of Pharmacy and Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1470-7192","authenticated-orcid":false,"given":"Andrea","family":"Angeli","sequence":"additional","affiliation":[{"name":"Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4262-0323","authenticated-orcid":false,"given":"Claudiu T.","family":"Supuran","sequence":"additional","affiliation":[{"name":"Neurofarba Department, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Sesto Fiorentino, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Luisi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rao, V., and Rao, L. (2015). Coumarins\u2014An Important Class of Phytochemicals. Phytochemicals\u2014Isolation, Characterisation and Role in Human Health, InTech. Chapter 5.","DOI":"10.5772\/58648"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/0306-3623(95)02112-4","article-title":"Pharmacological and biochemical actions of simple coumarins: Natural products with therapeutic potential","volume":"27","author":"Hoult","year":"1996","journal-title":"Gen. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5744","DOI":"10.1039\/D1NJ00614B","article-title":"4-Aminocoumarin derivatives: Synthesis and applications","volume":"45","author":"Sadeghpour","year":"2021","journal-title":"New J. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ejmech.2015.08.033","article-title":"Current developments of coumarin-based anti-cancer agents in medicinal chemistry","volume":"102","author":"Emami","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.3390\/molecules26020501","article-title":"Trending Topics on Coumarin and Its Derivatives in 2020","volume":"26","author":"Carneiro","year":"2021","journal-title":"Molecules"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1021\/jm801496u","article-title":"Synthesis, molecular modeling, and selective inhibitory activity against human monoamine oxidases of 3-carboxamido-7-substituted coumarins","volume":"52","author":"Chimenti","year":"2009","journal-title":"J. Med. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4846","DOI":"10.1016\/j.ejmech.2011.07.017","article-title":"Synthesis and selective human monoamine oxidase inhibition of 3-carbonyl, 3-acyl, and 3-carboxyhydrazido coumarin derivatives","volume":"46","author":"Secci","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/cbdv.200690017","article-title":"Lipophilicity plays a major role in modulating the inhibition of monoamine oxidase B by 7-substituted coumarins","volume":"3","author":"Carotti","year":"2006","journal-title":"Chem. Biodivers."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.ejmech.2017.11.061","article-title":"Inhibitory effects and structural insights for a novel series of coumarin-based compounds that selectively target human CA IX and CA XII carbonic anhydrases","volume":"143","author":"Mancuso","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"McDonald, P.C., Chafe, S.C., Supuran, C.T., and Dedhar, S. (2022). Cancer Therapeutic Targeting of Hypoxia Induced Carbonic Anhydrase IX: From Bench to Bedside. Cancers, 14.","DOI":"10.3390\/cancers14143297"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1080\/13543784.2021.2014813","article-title":"Carbonic anhydrase inhibitors: An update on experimental agents for the treatment and imaging of hypoxic tumors","volume":"30","author":"Supuran","year":"2021","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Marconi, G.D., Gallorini, M., Carradori, S., Guglielmi, P., Cataldi, A., and Zara, S. (2019). The Up-Regulation of Oxidative Stress as a Potential Mechanism of Novel MAO-B Inhibitors for Glioblastoma Treatment. Molecules, 24.","DOI":"10.3390\/molecules24102005"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbrc.2022.03.096","article-title":"Monoamine oxidase A drives neuroendocrine differentiation in prostate cancer","volume":"606","author":"Shui","year":"2022","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1172\/JCI70982","article-title":"Monoamine oxidase A mediates prostate tumorigenesis and cancer metastasis","volume":"124","author":"Wu","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.3390\/molecules27092887","article-title":"Design, Synthesis, and Biological Evaluation of Novel MAO-A Inhibitors Targeting Lung Cancer","volume":"27","author":"Bardaweel","year":"2022","journal-title":"Molecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.3109\/14756366.2015.1113173","article-title":"Synthesis and carbonic anhydrase inhibitory properties of amino acid\u2014Coumarin\/quinolinone conjugates incorporating glycine, alanine and phenylalanine moieties","volume":"31","author":"Tanc","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_17","unstructured":"Weinstein, B. (1983). Chemistry and Biochemistry of Amino Acids, Peptides and Proteins, Marcel Dekker, Inc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1002\/bip.360330709","article-title":"Conformational and topographical considerations in the design of biologically active peptides","volume":"33","author":"Hruby","year":"1993","journal-title":"Biopolymers"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/(SICI)1097-0282(1996)40:1<45::AID-BIP3>3.0.CO;2-3","article-title":"Crystal structures of peptides and modified peptides","volume":"40","author":"Marraud","year":"1996","journal-title":"Biopolymers"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/(SICI)1097-0282(19970415)41:5<555::AID-BIP7>3.0.CO;2-L","article-title":"Peptides containing the sulfonamide junction: Synthesis, structure, and conformation of Z-Tau-Pro-Phe-NHiPr","volume":"41","author":"Calcagni","year":"1997","journal-title":"Biopolymers"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"924","DOI":"10.3109\/14756366.2015.1070845","article-title":"Nitrobenzoxadiazole-based GSTP1-1 inhibitors containing the full peptidyl moiety of (pseudo)glutathione","volume":"31","author":"Luisi","year":"2016","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1399-3011.1995.tb01078.x","article-title":"Synthesis and activity of the glutathione analogue-(L-azaglutamyl)-L-cisteinyl-glycine","volume":"46","author":"Calcagni","year":"1995","journal-title":"Int. J. Peptide Prot. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3843","DOI":"10.1021\/ol0166552","article-title":"Unexpected stability of the urea cis-trans isomer in urea-containing model pseudopeptides","volume":"3","author":"Semetey","year":"2001","journal-title":"Org. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5219","DOI":"10.1016\/j.bmcl.2004.07.092","article-title":"Facile incorporation of urea pseudopeptides into protease substrate analogue inhibitors","volume":"14","author":"Myers","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5603","DOI":"10.1002\/ejoc.201500589","article-title":"A One-Pot Synthesis of Symmetrical and Unsymmetrical Dipeptide Ureas","volume":"2015","author":"Fayad","year":"2015","journal-title":"Eur. J. Org. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"105920","DOI":"10.1016\/j.bioorg.2022.105920","article-title":"A decade of tail-approach based design of selective as well as potent tumor associated carbonic anhydrase inhibitors","volume":"126","author":"Kumar","year":"2022","journal-title":"Bioorg. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1002\/ardp.19963291105","article-title":"Synthesis and activity of the glutathione analogue gamma-(L-gamma-oxaglutamyl)-L-cysteinyl-glycine","volume":"329","author":"Calcagni","year":"1996","journal-title":"Arch. Pharm. Pharm. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/nrd2467","article-title":"Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators","volume":"7","author":"Supuran","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1021\/ja809683v","article-title":"Non-zinc mediated inhibition of carbonic anhydrases: Coumarins are a new class of suicide inhibitors","volume":"131","author":"Maresca","year":"2009","journal-title":"J. Am. Chem. Soc."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1021\/jm901287j","article-title":"Deciphering the mechanism of carbonic anhydrase inhibition with coumarins and thiocoumarins","volume":"53","author":"Maresca","year":"2010","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1021\/ci400128m","article-title":"Improved docking of polypeptides with Glide","volume":"53","author":"Sherman","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"959","DOI":"10.3390\/ph14100959","article-title":"Discovery of a Novel Tetrapeptide Against Influenza A Virus: Rational Design, Synthesis, Bioactivity Evaluation and Computational Studies","volume":"14","author":"Scala","year":"2021","journal-title":"Pharmaceuticals"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Agamennone, M., and Superti, F. (2022). Broad-Spectrum Activity of Small Molecules Acting against Influenza A Virus: Biological and Computational Studies. Pharmaceuticals, 15.","DOI":"10.3390\/ph15030301"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2266","DOI":"10.1016\/j.bmc.2012.02.014","article-title":"Novel coumarins and 2-thioxo-coumarins as inhibitors of the tumor-associated carbonic anhydrases IX and XII","volume":"20","author":"Carta","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1021\/cr050262p","article-title":"Carbonic Anhydrase as a Model for Biophysical and Physical-Organic Studies of Proteins and Protein-Ligand Binding","volume":"108","author":"Krishnamurthy","year":"2008","journal-title":"Chem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"17889","DOI":"10.1073\/pnas.1114107108","article-title":"Mechanism of the hydrophobic effect in the biomolecular recognition of arylsulfonamides by carbonic anhydrase","volume":"108","author":"Snyder","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16233","DOI":"10.1073\/pnas.0908301106","article-title":"Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX","volume":"106","author":"Alterio","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.2174\/1871520622666220304184525","article-title":"Synthesis and biological evaluation of coumarin carboxamides as selective and potent inhibitors of carbonic anhydrases IX and XII","volume":"22","author":"Thacker","year":"2022","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"112650","DOI":"10.1016\/j.ejmech.2020.112650","article-title":"Chalcones: Unearthing their therapeutic possibility as monoamine oxidase B inhibitors","volume":"205","author":"Guglielmi","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"266","DOI":"10.2174\/0929867327666200121165931","article-title":"New aspects of monoamine oxidase B inhibitors: The key role of halogens to open the golden door","volume":"28","author":"Mathew","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105791","DOI":"10.1016\/j.bioorg.2022.105791","article-title":"Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase","volume":"123","author":"Bester","year":"2022","journal-title":"Bioorg. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1111\/cbdd.13919","article-title":"Deciphering the detailed structure-activity relationship of coumarins as Monoamine oxidase enzyme inhibitors\u2014An updated review","volume":"98","author":"Koyiparambath","year":"2021","journal-title":"Chem. Biol. Drug. Des."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1602\/neurorx.2.1.3","article-title":"The blood-brain barrier: Bottleneck in brain drug development","volume":"2","author":"Pardridge","year":"2005","journal-title":"NeuroRx"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"114828","DOI":"10.1016\/j.ejmech.2022.114828","article-title":"New \u03b2-arylchalcogeno amines with procognitive properties targeting Carbonic Anhydrases and Monoamine Oxidases","volume":"244","author":"Provensi","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1016\/S0021-9258(18)62326-9","article-title":"The carbon dioxide hydration activity of carbonic anhydrase","volume":"246","author":"Khalifah","year":"1971","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1021\/acs.jmedchem.9b01434","article-title":"1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin\/Isoxazole and Saccharin\/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors","volume":"63","author":"Secci","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1016\/S0021-9258(18)69497-9","article-title":"A rapid spectrophotometric assay of mono-amine oxidase based on the rate of disappearance of kynuramine","volume":"235","author":"Weissbach","year":"1960","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/cmdc.201500059","article-title":"Indanones as high-potency reversible inhibitors of monoamine oxidase","volume":"10","author":"Mostert","year":"2015","journal-title":"ChemMedChem"},{"key":"ref_49","unstructured":"Schr\u00f6dinger (2021). Schr\u00f6dinger Release 2021-4: Maestro, Glide, Prime, Desmond, Protein Preparation Wizard, Epik, SiteMap Schr\u00f6dinger, LLC."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Aided Mol. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1021\/jm030644s","article-title":"Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening","volume":"47","author":"Halgren","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Bowers, K.J., Chow, E., Xu, H., Dror, R.O., Eastwood, M.P., Gregersen, B.A., Klepeis, J.L., Kolossvary, I., Moraes, M.A., and Sacerdoti, F.D. (2006, January 11\u201317). Scalable Algorithms for Molecular Dynamics Simulations on Commodity Clusters. Proceedings of the ACM\/IEEE Conference on Supercomputing (SC06), Tampa, FL, USA.","DOI":"10.1109\/SC.2006.54"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1021\/ci800324m","article-title":"Identifying and characterizing binding sites and assessing druggability","volume":"49","author":"Halgren","year":"2009","journal-title":"J. Chem. Inf. Model."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1747-0285.2007.00483.x","article-title":"New method for fast and accurate binding-site identification and analysis","volume":"69","author":"Halgren","year":"2007","journal-title":"Chem. Biol. Drug Des."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/22\/7884\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:18:34Z","timestamp":1760145514000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/22\/7884"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,15]]},"references-count":55,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["molecules27227884"],"URL":"https:\/\/doi.org\/10.3390\/molecules27227884","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,15]]}}}