{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:45:48Z","timestamp":1784875548006,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T00:00:00Z","timestamp":1694217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NextGenerationEU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["PE00000007, INF-ACT"],"award-info":[{"award-number":["PE00000007, INF-ACT"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pseudomonas aeruginosa (PA), one of the ESKAPE pathogens, is an opportunistic Gram-negative bacterium responsible for nosocomial infections in humans but also for infections in patients affected by AIDS, cancer, or cystic fibrosis (CF). Treatment of PA infections in CF patients is a global healthcare problem due to the ability of PA to gain antibiotic tolerance through biofilm formation. Anti-virulence compounds represent a promising approach as adjuvant therapy, which could reduce or eliminate the pathogenicity of PA without impacting its growth. Pyocyanin is one of the virulence factors whose production is modulated by the Pseudomonas quinolone signal (PQS) through its receptor PqsR. Different PqsR modulators have been synthesized over the years, highlighting this new powerful therapeutic strategy. Based on the promising structure of quinazolin-4(3H)-one, we developed compounds 7a\u2013d, 8a,b, 9, 10, and 11a\u2013f able to reduce biofilm formation and the production of virulence factors (pyocyanin and pyoverdine) at 50 \u00b5M in two PA strains responsible for CF acute and chronic infections. The developed compounds did not reduce the cell viability of IB3-1 bronchial CF cells, and computational studies confirmed the potential ability of novel compounds to act as potential Pqs system modulators.<\/jats:p>","DOI":"10.3390\/molecules28186535","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T09:11:18Z","timestamp":1694423478000},"page":"6535","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Development of Quinazolinone Derivatives as Modulators of Virulence Factors of Pseudomonas aeruginosa Cystic Fibrosis Strains"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1619-3295","authenticated-orcid":false,"given":"Gabriele","family":"Carullo","sequence":"first","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5850-2810","authenticated-orcid":false,"given":"Giovanni","family":"Di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8240-6519","authenticated-orcid":false,"given":"Sara","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Lupetti","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Tudino","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9375-6242","authenticated-orcid":false,"given":"Simone","family":"Brogi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8471-0880","authenticated-orcid":false,"given":"Stefania","family":"Butini","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Campiani","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8313-2417","authenticated-orcid":false,"given":"Sandra","family":"Gemma","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Chemistry and Pharmacy, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6309-6981","authenticated-orcid":false,"given":"Arianna","family":"Pompilio","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, School of Medicine and Health Sciences \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1023523","DOI":"10.3389\/fmicb.2022.1023523","article-title":"Pseudomonas aeruginosa reference strains PAO1 and PA14: A genomic, phenotypic, and therapeutic review","volume":"13","author":"Grace","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.biotechadv.2018.11.013","article-title":"Antibiotic Resistance in Pseudomonas aeruginosa: Mechanisms and Alternative Therapeutic Strategies","volume":"37","author":"Pang","year":"2019","journal-title":"Biotechnol. Adv."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Karruli, A., Catalini, C., D\u2019amore, C., Foglia, F., Mari, F., Harxhi, A., Galdiero, M., and Durante-Mangoni, E. (2023). Evidence-Based Treatment of Pseudomonas aeruginosa Infections: A Critical Reappraisal. Antibiotics, 12.","DOI":"10.3390\/antibiotics12020399"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Li, D., and Schneider-Futschik, E.K. (2023). Current and Emerging Inhaled Antibiotics for Chronic Pulmonary Pseudomonas aeruginosa and Staphylococcus aureus Infections in Cystic Fibrosis. Antibiotics, 12.","DOI":"10.3390\/antibiotics12030484"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1104856","DOI":"10.3389\/fphys.2023.1104856","article-title":"To bead or not to bead: A review of Pseudomonas aeruginosa lung infection models for cystic fibrosis","volume":"14","author":"Reyne","year":"2023","journal-title":"Front. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105461","DOI":"10.1016\/j.micpath.2022.105461","article-title":"Prevalence of antibiotic resistance of Pseudomonas aeruginosa in cystic fibrosis infection: A systematic review and meta-analysis","volume":"165","author":"Bonyadi","year":"2022","journal-title":"Microb. Pathog."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5103","DOI":"10.1038\/s41467-022-32833-9","article-title":"Tackling recalcitrant Pseudomonas aeruginosa infections in critical illness via anti-virulence monotherapy","volume":"13","author":"Singh","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10385","DOI":"10.1021\/acs.jmedchem.8b00540","article-title":"Pseudomonas aeruginosa Quorum Sensing Systems as Drug Discovery Targets: Current Position and Future Perspectives","volume":"61","author":"Soukarieh","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jurado-Mart\u00edn, I., Sainz-Mej\u00edas, M., and McClean, S. (2021). Pseudomonas aeruginosa: An Audacious Pathogen with an Adaptable Arsenal of Virulence Factors. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063128"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejmech.2019.03.049","article-title":"Anti-PqsR compounds as next-generation antibacterial agents against Pseudomonas aeruginosa: A review","volume":"172","author":"Soheili","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1039\/b803796p","article-title":"Quorum sensing by 2-alkyl-4-quinolones in Pseudomonas aeruginosa and other bacterial species","volume":"4","author":"Dubern","year":"2008","journal-title":"Mol. Biosyst."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/j.1365-2958.2004.04448.x","article-title":"The contribution of MvfR to Pseudomonas aeruginosa pathogenesis and quorum sensing circuitry regulation: Multiple quorum sensing-regulated genes are modulated without affecting lasRI, rhlRI or the production of N-acyl- l-homoserine lactones","volume":"55","author":"Gopalan","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"10921","DOI":"10.1021\/acs.jmedchem.0c00763","article-title":"Novel 2-Substituted 3-Hydroxy-1,6-Dimethylpyridin-4(1H)-Ones as Dual-Acting Biofilm Inhibitors of Pseudomonas aeruginosa","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1021\/acs.jmedchem.1c01781","article-title":"New Pqs Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant Pseudomonas aeruginosa","volume":"65","author":"Liu","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e2204443","DOI":"10.1002\/advs.202204443","article-title":"Towards Translation of PqsR Inverse Agonists: From In Vitro Efficacy Optimization to In Vivo Proof-of-Principle","volume":"10","author":"Hamed","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ilangovan, A., Fletcher, M., Rampioni, G., Pustelny, C., Rumbaugh, K., Heeb, S., C\u00e1mara, M., Truman, A., Chhabra, S.R., and Emsley, J. (2013). Structural Basis for Native Agonist and Synthetic Inhibitor Recognition by the Pseudomonas aeruginosa Quorum Sensing Regulator PqsR (MvfR). PLOS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003508"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1021\/acsinfecdis.1c00175","article-title":"Design and Evaluation of New Quinazolin-4(3H)-one Derived PqsR Antagonists as Quorum Sensing Quenchers in Pseudomonas aeruginosa","volume":"7","author":"Soukarieh","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"112778","DOI":"10.1016\/j.ejmech.2020.112778","article-title":"Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR","volume":"208","author":"Grossman","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Munir, R., Javid, N., Zia-Ur-Rehman, M., Zaheer, M., Huma, R., Roohi, A., and Athar, M.M. (2021). Synthesis of Novel N-Acylhydrazones and Their C-N\/N-N Bond Conformational Characterization by NMR Spectroscopy. Molecules, 26.","DOI":"10.3390\/molecules26164908"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"197475","DOI":"10.1155\/2013\/197475","article-title":"Synthesis and Conformational Assignment of N-(E)-Stilbenyloxymethylenecarbonyl-Substituted Hydrazones of Acetone and o-(m- and p-) Chloro- (nitro-) benzaldehydes by Means of 1H and 13C NMR Spectroscopy","volume":"2013","author":"Patorski","year":"2013","journal-title":"J. Spectrosc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1002\/cmdc.201900621","article-title":"Flexible Fragment Growing Boosts Potency of Quorum-Sensing Inhibitors against Pseudomonas aeruginosa Virulence","volume":"15","author":"Zender","year":"2020","journal-title":"ChemMedChem"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3389\/fchem.2020.00204","article-title":"Hit Identification of New Potent PqsR Antagonists as Inhibitors of Quorum Sensing in Planktonic and Biofilm Grown Pseudomonas aeruginosa","volume":"8","author":"Soukarieh","year":"2020","journal-title":"Front. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"113797","DOI":"10.1016\/j.ejmech.2021.113797","article-title":"Divergent synthesis and biological evaluation of 2-(trifluoromethyl)pyridines as virulence-attenuating inverse agonists targeting PqsR","volume":"226","author":"Hodzic","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e02158-17","DOI":"10.1128\/mBio.02158-17","article-title":"Molecular Insights into Function and Competitive Inhibition of Pseudomonas aeruginosa Multiple Virulence Factor Regulator","volume":"9","author":"Kitao","year":"2018","journal-title":"mBio"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.chembiol.2022.02.007","article-title":"A Pseudomonas aeruginosa PQS quorum-sensing system inhibitor with anti-staphylococcal activity sensitizes polymicrobial biofilms to tobramycin","volume":"29","author":"Murray","year":"2022","journal-title":"Cell Chem. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19725","DOI":"10.1039\/D1TA02792A","article-title":"Three-in-one: Achieving a robust and effective hydrogen-evolving hybrid material by integrating polyoxometalate, a photo-responsive metal\u2013organic framework, and in situ generated Pt nanoparticles","volume":"9","author":"Jiao","year":"2021","journal-title":"J. Mater. Chem. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9752","DOI":"10.1021\/acs.jmedchem.0c00917","article-title":"Design, Synthesis, and Evaluation of New Quinazolinone Derivatives that Inhibit Bloom Syndrome Protein (BLM) Helicase, Trigger DNA Damage at the Telomere Region, and Synergize with PARP Inhibitors","volume":"63","author":"Wang","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1134\/S1070428009060190","article-title":"Fluorine-containing heterocycles: XIX. Synthesis of fluorine-containing quinazolin-4-ones from 3,1-benzoxazin-4-ones","volume":"45","author":"Laeva","year":"2009","journal-title":"Russ. J. Org. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.ejmech.2014.09.028","article-title":"Development of 2-(4-oxoquinazolin-3(4H)-yl)acetamide derivatives as novel enoyl-acyl carrier protein reductase (InhA) inhibitors for the treatment of tuberculosis","volume":"86","author":"Pedgaonkar","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5596816","DOI":"10.1155\/2021\/5596816","article-title":"Green Synthesis of New Pyrrolo [1,2-a] quinoxalines as Antiproliferative Agents in GPER-expressing Breast Cancer Cells","volume":"2021","author":"Carullo","year":"2021","journal-title":"J. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1002\/cmdc.201700145","article-title":"Identification of Breast Cancer Inhibitors Specific for G Protein-Coupled Estrogen Receptor (GPER)-Expressing Cells","volume":"12","author":"Aiello","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3261","DOI":"10.1099\/mic.0.29175-0","article-title":"Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis","volume":"152","author":"Bragonzi","year":"2006","journal-title":"Microbiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1016\/S0169-409X(02)00152-7","article-title":"Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: Rethinking antibiotic treatment strategies and drug targets","volume":"54","author":"Hassett","year":"2002","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1172\/JCI0213870","article-title":"Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients","volume":"109","author":"Worlitzsch","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1099\/jmm.0.45969-0","article-title":"Microcolony formation: A novel biofilm model of Pseudomonas aeruginosa for the cystic fibrosis lung","volume":"54","author":"Sriramulu","year":"2005","journal-title":"J. Med. Microbiol."},{"key":"ref_36","unstructured":"(2019). Performance Standards for Antimicrobial Susceptibility Testing (Standard No. CLSI M100-ED29)."},{"key":"ref_37","unstructured":"(2023, April 18). Gradwohl\u2019s Clinical Laboratory Methods and Diagnosis|WorldCat.Org. Available online: https:\/\/www.worldcat.org\/it\/title\/gradwohls-clinical-laboratory-methods-and-diagnosis\/oclc\/36904373."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1128\/jb.172.2.884-900.1990","article-title":"Identification and characterization of genes for a second anthranilate synthase in Pseudomonas aeruginosa: Interchangeability of the two anthranilate synthases and evolutionary implications","volume":"172","author":"Essar","year":"1990","journal-title":"J. Bacteriol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Di Bonaventura, G., Lupetti, V., De Fabritiis, S., Piccirilli, A., Porreca, A., Di Nicola, M., and Pompilio, A. (2022). Giving Drugs a Second Chance: Antibacterial and Antibiofilm Effects of Ciclopirox and Ribavirin against Cystic Fibrosis Pseudomonas aeruginosa Strains. Int. J. Mol. Sci., 23.","DOI":"10.20944\/preprints202204.0212.v1"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e202200456","DOI":"10.1002\/cmdc.202200456","article-title":"Synthesis of Unsymmetrical Squaramides as Allosteric GSK-3\u03b2 Inhibitors Promoting \u03b2-Catenin-Mediated Transcription of TCF\/LEF in Retinal Pigment Epithelial Cells","volume":"17","author":"Carullo","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e202200050","DOI":"10.1002\/cmdc.202200050","article-title":"Design and Synthesis of Oligopeptidic Parvulin Inhibitors","volume":"17","author":"Relitti","year":"2022","journal-title":"ChemMedChem"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"114409","DOI":"10.1016\/j.ejmech.2022.114409","article-title":"Azetidin-2-one-based small molecules as dual hHDAC6\/HDAC8 inhibitors: Investigation of their mechanism of action and impact of dual inhibition profile on cell viability","volume":"238","author":"Federico","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3389\/fchem.2019.00574","article-title":"Identification of Novel 3-Hydroxy-pyran-4-One Derivatives as Potent HIV-1 Integrase Inhibitors Using in silico Structure-Based Combinatorial Library Design Approach","volume":"7","author":"Sirous","year":"2019","journal-title":"Front. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1063\/1.445869","article-title":"Comparison of simple potential functions for simulating liquid water","volume":"79","author":"Jorgensen","year":"1983","journal-title":"J. Chem. Phys."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1103\/PhysRevA.31.1695","article-title":"Canonical dynamics: Equilibrium phase-space distributions","volume":"31","author":"Hoover","year":"1985","journal-title":"Phys. Rev. A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8577","DOI":"10.1063\/1.470117","article-title":"A smooth particle mesh Ewald method","volume":"103","author":"Essmann","year":"1995","journal-title":"J. Chem. Phys."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/18\/6535\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:50Z","timestamp":1760129270000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/18\/6535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,9]]},"references-count":48,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["molecules28186535"],"URL":"https:\/\/doi.org\/10.3390\/molecules28186535","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,9]]}}}