{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:37:28Z","timestamp":1792805848926,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Module fund given by the Aga Khan University Medical College"},{"name":"Akbarali Habib Bandeali"},{"name":"Hamdard University research committee","id":[{"id":"https:\/\/ror.org\/01zrv0z61","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>(1) Background: Staphylococcus aureus (S. aureus) is one of the most frequent causes of biofilm-associated infections. With the emergence of antibiotic-resistant, especially methicillin-resistant S. aureus (MRSA), there is an urgent need to discover novel inhibitory compounds against this clinically important pathogen. In this study, we evaluated the antimicrobial and anti-biofilm activity of 11 compounds, including phenyl propenes and phenolic aldehydes, eugenol, ferulic acid, sinapic acid, salicylaldehyde, vanillin, cinnamoyl acid, and aldehydes, against drug-resistant S. aureus isolates. (2) Methods: Thirty-two clinical S. aureus isolates were obtained from Alkhidmat Diagnostic Center and Blood Bank, Karachi, Pakistan, and screened for biofilm-forming potential, and susceptibility\/resistance against ciprofloxacin, chloramphenicol, ampicillin, amikacin, cephalothin, clindamycin, streptomycin, and gentamicin using the Kirby-Bauer disk diffusion method. Subsequently, 5 representative clinical isolates were selected and used to test the antimicrobial and anti-biofilm potential of 11 compounds using both qualitative and quantitative assays, followed by qPCR analysis to examine the differences in the expression levels of biofilm-forming genes (ica-A, fnb-B, clf-A and cna) in treated (with natural compounds and their derivatives) and untreated isolates. (3) Results: All isolates were found to be multi-drug resistant and dominant biofilm formers. The individual Minimum Inhibitory Concentration (MIC) of natural compounds and their analogues ranged from 0.75\u2013160 mg\/mL. Furthermore, the compounds, Salicylaldehyde (SALI), Vanillin (VAN), \u03b1-methyl-trans-cinnamaldehyde (A-MT), and trans-4-nitrocinnamic acid (T4N) exhibited significant (15\u201392%) biofilm inhibition\/reduction percentage capacity at the concentration of 1\u201310 mg\/mL. Gene expression analysis showed that salicylaldehyde, \u03b1-methyl-trans-cinnamaldehyde, and \u03b1-bromo-trans-cinnamaldehyde resulted in a significant (p &lt; 0.05) downregulation of the expression of ica-A, clf-A, and fnb-A genes compared to the untreated resistant isolate. (4) Conclusions: The natural compounds and their analogues used in this study exhibited significant antimicrobial and anti-biofilm activity against S. aureus. Biofilms persist as the main concern in clinical settings. These compounds may serve as potential candidate drug molecules against biofilm forming S. aureus.<\/jats:p>","DOI":"10.3390\/molecules27206874","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T22:21:11Z","timestamp":1665699671000},"page":"6874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["Analysis of the Antimicrobial and Anti-Biofilm Activity of Natural Compounds and Their Analogues against Staphylococcus aureus Isolates"],"prefix":"10.3390","volume":"27","author":[{"given":"Sobia","family":"Mastoor","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Karachi, Karachi 75270, Pakistan"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Karachi 74600, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fizza","family":"Nazim","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Rizwan-ul-Hasan","sequence":"additional","affiliation":[{"name":"Department of Computer Science, DHA Suffa University, Karachi 75500, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shabnam","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Nawazish","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, University of Karachi, Karachi 75270, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9497-0902","authenticated-orcid":false,"given":"Syed Hani","family":"Abidi","sequence":"additional","affiliation":[{"name":"Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan"},{"name":"Department of Biomedical Sciences, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jhin.2009.07.004","article-title":"Community-associated meticillin-resistant Staphylococcus aureus as a cause of hospital-acquired infections","volume":"73","author":"Skov","year":"2009","journal-title":"J. Hosp. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1097\/MCP.0000000000000518","article-title":"Staphylococcus aureus in cystic fibrosis: Pivotal role or bit part actor?","volume":"24","author":"Hurley","year":"2018","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.micpath.2015.11.009","article-title":"High potential of adhesion to biotic and abiotic surfaces by opportunistic Staphylococcus aureus strains isolated from orthodontic appliances","volume":"91","author":"Merghni","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.2217\/fmb.09.102","article-title":"Structural and functional role of Staphylococcus aureus surface components recognizing adhesive matrix molecules of the host","volume":"4","author":"Speziale","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1574-6968.2004.tb09643.x","article-title":"What drives bacteria to produce a biofilm?","volume":"236","author":"Jefferson","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.tim.2011.06.004","article-title":"Staphylococcal biofilm disassembly","volume":"19","author":"Boles","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Uru\u00e9n, C., Chopo-Escuin, G., Tommassen, J., Mainar-Jaime, R.C., and Arenas, J. (2020). Biofilms as promoters of bacterial antibiotic resistance and tolerance. Antibiotics, 10.","DOI":"10.3390\/antibiotics10010003"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.17485\/ijst\/2009\/v2i12.5","article-title":"Incidence of methicillin resistant Staphylococcus aureus (MRSA) from septicemia suspected children","volume":"2","author":"Saravanan","year":"2009","journal-title":"Indian J. Sci. Technol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"114614","DOI":"10.1016\/j.jep.2021.114614","article-title":"History, phytochemistry, experimental pharmacology and clinical uses of honey: A comprehensive review with special reference to Unani medicine","volume":"282","author":"Nikhat","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104675","DOI":"10.1016\/j.fitote.2020.104675","article-title":"Traditional uses, phytochemistry and pharmacological activities of the genus Cinnamomum (Lauraceae): A review","volume":"146","author":"Wang","year":"2020","journal-title":"Fitoterapia"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Deryabin, D., Galadzhieva, A., Kosyan, D., and Duskaev, G. (2019). Plant-derived inhibitors of AHL-mediated quorum sensing in bacteria: Modes of action. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225588"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1263\/jbb.99.78","article-title":"Estimation of the biofilm formation of Escherichia coli K-12 by the cell number","volume":"99","author":"Narisawa","year":"2005","journal-title":"J. Biosci. Bioeng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2660","DOI":"10.1002\/jrs.6237","article-title":"Correlation of crystal violet biofilm test results of Staphylococcus aureus clinical isolates with Raman spectroscopic read-out","volume":"52","author":"Ebert","year":"2021","journal-title":"J. Raman Spectrosc."},{"key":"ref_14","first-page":"Doc07","article-title":"Detection of genes involved in biofilm formation in Staphylococcus aureus isolates","volume":"11","author":"Nourbakhsh","year":"2016","journal-title":"GMS Hyg. Infect. Control"},{"key":"ref_15","first-page":"34","article-title":"Prevalence and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus: A multicentre study","volume":"24","author":"Rajaduraipandi","year":"2006","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1289\/ehp.9585","article-title":"Isolation of Staphylococcus aureus and antibiotic-resistant Staphylococcus aureus from residential indoor bioaerosols","volume":"114","author":"Gandara","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.apjtm.2017.10.003","article-title":"Antimicrobial resistance and underlying mechanisms in Staphylococcus aureus isolates","volume":"10","year":"2017","journal-title":"Asian Pac. J. Trop. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.nmni.2015.05.003","article-title":"Epidemiology of Staphylococcus aureus in Bangalore, India: Emergence of the ST217 clone and high rate of resistance to erythromycin and ciprofloxacin in the community","volume":"7","author":"Bouchiat","year":"2015","journal-title":"New Microbes New Infect."},{"key":"ref_19","first-page":"42306","article-title":"High prevalence of ciprofloxacin resistance in community associated Staphylococcus aureus in a tertiary care Indian hospital","volume":"2014","author":"Chakrakodi","year":"2014","journal-title":"Adv. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1B.1.1","DOI":"10.1002\/9780471729259.mc01b01s22","article-title":"Growing and analyzing static biofilms","volume":"22","author":"Merritt","year":"2011","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref_21","first-page":"2776","article-title":"Analysis of anti-microbial and anti-biofilm activity of hand washes and sanitizers against S. aureus and P. aeruginosa","volume":"2019","author":"Ahmed","year":"2020","journal-title":"J Pak Med Assoc"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Abidi, S.H., Sherwani, S.K., Siddiqui, T.R., Bashir, A., and Kazmi, S.U. (2013). Drug resistance profile and biofilm forming potential of Pseudomonas aeruginosa isolated from contact lenses in Karachi-Pakistan. BMC Ophthalmol., 13.","DOI":"10.1186\/1471-2415-13-57"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.bjid.2018.03.003","article-title":"Biofilm production by clinical isolates of Pseudomonas aeruginosa and structural changes in LasR protein of isolates non biofilm-producing","volume":"22","author":"Lima","year":"2018","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.ijmm.2018.09.005","article-title":"Comparative analyses of biofilm formation among different Cutibacterium acnes isolates","volume":"308","author":"Kuehnast","year":"2018","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00084-16","DOI":"10.1128\/CMR.00084-16","article-title":"Options and limitations in clinical investigation of bacterial biofilms","volume":"31","author":"Magana","year":"2018","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"160","DOI":"10.24171\/j.phrp.2018.9.4.04","article-title":"Evaluation of biofilm formation and presence of ica genes in Staphylococcus epidermidis clinical isolates","volume":"9","author":"Kord","year":"2018","journal-title":"Osong Public Health Res. Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"309","DOI":"10.4103\/JLP.JLP_122_17","article-title":"Association of intercellular adhesion gene A with biofilm formation in staphylococci isolates from patients with conjunctivitis","volume":"10","author":"Elkhashab","year":"2018","journal-title":"J. Lab. Physicians"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"He, S., Zhan, Z., Shi, C., Wang, S., and Shi, X. (2022). Ethanol at subinhibitory concentrations enhances biofilm formation in Salmonella enteritidis. Foods, 11.","DOI":"10.3390\/foods11152237"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1672","DOI":"10.2174\/092986711795471347","article-title":"Cinnamic acid derivatives as anticancer agents-a review","volume":"18","author":"De","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_30","first-page":"68","article-title":"Synthesis and radical scavenging activity of cinnamic acid esters","volume":"1","author":"Chochkova","year":"2017","journal-title":"Bulg. Chem. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1080\/1040841X.2017.1295225","article-title":"Antimicrobial activity of eugenol and essential oils containing eugenol: A mechanistic viewpoint","volume":"43","author":"Marchese","year":"2017","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1080\/14786419.2017.1342083","article-title":"Salicylaldehyde and dihydroisobenzofuran derivatives from the marine fungus Zopfiella marina","volume":"32","author":"Chokpaiboon","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1021\/jf048575t","article-title":"Structure\u2212function analysis of the vanillin molecule and its antifungal properties","volume":"53","author":"Fitzgerald","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"El-Saber Batiha, G., Alkazmi, L.M., Wasef, L.G., Beshbishy, A.M., Nadwa, E.H., and Rashwan, E.K. (2020). Syzygium aromaticum L. (Myrtaceae): Traditional uses, bioactive chemical constituents, pharmacological and toxicological activities. Biomolecules, 10.","DOI":"10.3390\/biom10020202"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sharma, A., Shahzad, B., Rehman, A., Bhardwaj, R., Landi, M., and Zheng, B. (2019). Response of phenylpropanoid pathway and the role of polyphenols in plants under abiotic stress. Molecules, 24.","DOI":"10.3390\/molecules24132452"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Ali, I.A., Matinlinna, J.P., L\u00e9vesque, C.M., and Neelakantan, P. (2021). Trans-cinnamaldehyde attenuates Enterococcus faecalis virulence and inhibits biofilm formation. Antibiotics, 10.","DOI":"10.1101\/2021.03.15.435450"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/09687630701539350","article-title":"A comprehensive review on vanilla flavor: Extraction, isolation and quantification of vanillin and others constituents","volume":"59","author":"Sinha","year":"2008","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/1541-4337.12041","article-title":"Sinapic acid and its derivatives: Natural sources and bioactivity","volume":"13","year":"2014","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Osman, M.F., Mohd Hassan, N., Khatib, A., and Tolos, S.M. (2018). Antioxidant activities of Dialium indum L. Fruit and gas chromatography-mass spectrometry (GC-MS) of the active fractions. Antioxidants, 7.","DOI":"10.3390\/antiox7110154"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"919","DOI":"10.3906\/sag-1406-112","article-title":"Antibiofilm activity of trans-cinnamaldehyde, p-coumaric, and ferulic acids on uropathogenic Escherichia coli","volume":"45","author":"Kot","year":"2015","journal-title":"Turk. J. Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1021\/jf011348w","article-title":"Antioxidant properties of ferulic acid and its related compounds","volume":"50","author":"Kikuzaki","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kim, Y., Kim, S., Cho, K.-H., Lee, J.-H., and Lee, J. (2022). Antibiofilm activities of cinnamaldehyde analogs against Uropathogenic Escherichia coli and Staphylococcus aureus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137225"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ejmech.2006.11.010","article-title":"Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde","volume":"42","author":"Shi","year":"2007","journal-title":"Eur. J. Med. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s00044-013-0672-7","article-title":"Synthesis and anti-biofilm activity of thiazole Schiff bases","volume":"23","author":"More","year":"2014","journal-title":"Med. Chem. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17943","DOI":"10.3390\/molecules191117943","article-title":"Efficiency of vanilla, patchouli and ylang ylang essential oils stabilized by iron oxide@ C14 nanostructures against bacterial adherence and biofilms formed by Staphylococcus aureus and Klebsiella pneumoniae clinical strains","volume":"19","author":"Bilcu","year":"2014","journal-title":"Molecules"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00253-012-4091-3","article-title":"Study on carvacrol and cinnamaldehyde polymeric films: Mechanical properties, release kinetics and antibacterial and antibiofilm activities","volume":"96","author":"Nostro","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.ibiod.2018.06.003","article-title":"Evaluation of cinnamaldehyde and cinnamic acid derivatives in microbial growth control","volume":"141","author":"Malheiro","year":"2019","journal-title":"Int. Biodeterior. Biodegrad."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00430-002-0124-3","article-title":"Evaluation of different detection methods of biofilm formation in Staphylococcus aureus","volume":"191","author":"Knobloch","year":"2002","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Achek, R., Hotzel, H., Nabi, I., Kechida, S., Mami, D., Didouh, N., Tomaso, H., Neubauer, H., Ehricht, R., and Monecke, S. (2020). Phenotypic and molecular detection of biofilm formation in Staphylococcus aureus isolated from different sources in Algeria. Pathogens, 9.","DOI":"10.3390\/pathogens9020153"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Dro\u017cd\u017c, K., Ocho\u0144ska, D., \u015acibik, \u0141., Go\u0142da-C\u0119pa, M., Biegun, K., and Brzychczy-W\u0142och, M. (2022). The Frequency of Occurrence of Resistance and Genes Involved in the Process of Adhesion and Accumulation of Biofilm in Staphylococcus aureus Strains Isolated from Tracheostomy Tubes. Microorganisms, 10.","DOI":"10.3390\/microorganisms10061210"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Haddad, O., Merghni, A., Elargoubi, A., Rhim, H., Kadri, Y., and Mastouri, M. (2018). Comparative study of virulence factors among methicillin resistant Staphylococcus aureus clinical isolates. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3457-2"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1086\/420851","article-title":"Virulence potential of the staphylococcal adhesin CNA in experimental arthritis is determined by its affinity for collagen","volume":"189","author":"Xu","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"K\u0131rmusao\u011flu, S. (2019). The methods for detection of biofilm and screening antibiofilm activity of agents. Antimicrobials, Antibiotic Resistance, Antibiofilm Strategies and Activity Methods, IntechOpen.","DOI":"10.5772\/intechopen.84411"},{"key":"ref_54","first-page":"54","article-title":"Chemical composition and antibacterial, anti-biofilm and anti-virulence activities of plant extracts against human pathogenic bacteria","volume":"12","author":"Mulat","year":"2022","journal-title":"Nat. Prod. J."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6874\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:36Z","timestamp":1760144016000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":54,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27206874"],"URL":"https:\/\/doi.org\/10.3390\/molecules27206874","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,13]]}}}