{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T05:31:41Z","timestamp":1773898301172,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Propenylbenzenes, including isosafrole, anethole, isoeugenol, and their derivatives, are natural compounds found in essential oils from various plants. Compounds of this group are important and valuable, and are used in the flavour and fragrance industries as well as the pharmaceutical and cosmetic industries. The aim of this study was to develop an efficient process for synthesising oxygenated derivatives of these compounds and evaluate their potential biological activities. In this paper, we propose a two-step chemo-enzymatic method. The first step involves the synthesis of corresponding diols <jats:bold>1b\u20135b<\/jats:bold> from propenylbenzenes <jats:bold>1a\u20135a<\/jats:bold><jats:italic>via<\/jats:italic> lipase catalysed epoxidation followed by epoxide hydrolysis. The second step involves the microbial oxidation of a diasteroisomeric mixture of diols <jats:bold>1b\u20135b<\/jats:bold> to yield the corresponding hydroxy ketones <jats:bold>1c\u20134c<\/jats:bold>, which in this study was performed on a preparative scale using <jats:italic>Dietzia<\/jats:italic> sp. DSM44016, <jats:italic>Rhodococcus erythropolis<\/jats:italic> DSM44534, <jats:italic>R. erythropolis<\/jats:italic> PCM2150, and <jats:italic>Rhodococcus ruber<\/jats:italic> PCM2166. Application of scaled-up processes allowed to obtain hydroxy ketones <jats:bold>1-4c<\/jats:bold> with the following yield range 36\u201362.5%. The propenylbenzene derivatives thus obtained and the starting compounds were tested for various biological activities, including antimicrobial, antioxidant, haemolytic, and anticancer activities, and their impact on membrane fluidity. Fungistatic activity assay against selected strains of <jats:italic>Candida albicans<\/jats:italic> results in MIC<jats:sub>50<\/jats:sub> value varied from 37 to 124\u2009\u03bcg\/mL for compounds <jats:bold>1a<\/jats:bold>, <jats:bold>3a\u2013c<\/jats:bold>, <jats:bold>4a,b<\/jats:bold>, and <jats:bold>5a,b<\/jats:bold>. The highest antiradical activity was shown by propenylbenzenes <jats:bold>1-5a<\/jats:bold> with a double bond in their structure with EC<jats:sub>50<\/jats:sub> value ranged from 19 to 31\u2009\u03bcg\/mL. Haemolytic activity assay showed no cytotoxicity of the tested compounds on human RBCs whereas, compounds <jats:bold>2b\u20134b<\/jats:bold> and <jats:bold>2c\u20134c<\/jats:bold> affected the fluidity of the RBCs membrane. The tested compounds depending on their concentration showed different antiproliferative activity against HepG2, Caco-2, and MG63. The results indicate the potential utility of these compounds as fungistatics, antioxidants, and proliferation inhibitors of selected cell lines.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1223123","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T06:41:08Z","timestamp":1687761668000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Chemo-enzymatic synthesis and biological activity evaluation of propenylbenzene derivatives"],"prefix":"10.3389","volume":"14","author":[{"given":"Dawid","family":"Hernik","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewa","family":"Szczepa\u0144ska","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Ghezzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Brenna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"W\u0142och","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Pruchnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malwina","family":"Mularczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Marycz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Olejniczak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filip","family":"Boraty\u0144ski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/978-3-319-41342-6_11","article-title":"Anethole and its role in chronic diseases","volume":"929","author":"Aprotosoaie","year":"2016","journal-title":"Adv Exp. Med. Biol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1016\/j.tiv.2005.04.012","article-title":"A comparative study of the antioxidant\/prooxidant activities of eugenol and isoeugenol with various concentrations and axidation conditions","volume":"19","author":"Atsumi","year":"2005","journal-title":"Toxicol. In Vitro"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/jobm.201100272","article-title":"Proton pumping ATPase mediated fungicidal activity of two essential oil components","volume":"51","author":"Bhatia","year":"2011","journal-title":"J. Basic Microbiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1039\/C39900001301","article-title":"Lipase-mediated formation of peroxycarboxylic acids used in catalytic epoxidation of alkenes","volume":"19","author":"Bj\u00f6rkling","year":"1990","journal-title":"J. Chem. Soc. Chem. Commun."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"104271","DOI":"10.1016\/j.arabjc.2022.104271","article-title":"Chemical composition, antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile, study in vitro and in silico","volume":"15","author":"Bruna","year":"2022","journal-title":"Arab. J. Chem."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.lfs.2014.07.022","article-title":"Effects of the essential oil of Croton zehntneri and its major components, anethole and estragole, on the rat corpora cavernosa","volume":"112","author":"Cabral","year":"2014","journal-title":"Life Sci."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"3600","DOI":"10.1021\/jo00066a002","article-title":"Selective oxidation of optically active sec,sec-1,2-diols by dioxiranes. A practical method for the synthesis of homochiral \u03b1-hydroxy ketones in high optical purity","volume":"58","author":"D\u2019Accolti","year":"1993","journal-title":"J. Org. Chem."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"5432","DOI":"10.3390\/ijms23105432","article-title":"Analitical and theoretical studies of antioxidant properties of chosen anthocyanins; a structure-dependent relationship","volume":"23","author":"Dudek","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12906-021-03324-z","article-title":"Biological evaluation of safrole oil and safrole oil nanoemulgel as antioxidant, antibacterial, antifungal and anticancer","volume":"21","author":"Eid","year":"2021","journal-title":"BMC Complement. Med. Ther."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1002\/14356007.a11_141","article-title":"Flavors and fragrances","author":"Fahlbusch","year":"2003","journal-title":"Ullmann\u2019s Encyclopedia of Industrial Chemistry"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"7600","DOI":"10.3390\/ijms22147600","article-title":"Microbial synthesis and evaluation of fungistatic activity of 3-butyl-3-hydroxyphthalide, the mammalian metabolite of 3-n-butylidenephthalide","volume":"22","author":"Gach","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1012","DOI":"10.4067\/S0717-95022011000300059","article-title":"Comparison of behavior, morphology and morphometry of equine and canine adipose derived mesenchymal stem cells in culture","volume":"29","author":"Grzesiak","year":"2011","journal-title":"Int. J. Morphol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"5462","DOI":"10.1021\/acs.chemrev.5b00052","article-title":"Isomerization of allylbenzenes","volume":"115","author":"Hassam","year":"2015","journal-title":"Chem. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1002\/jsfa.5633","article-title":"High-throughput micro plate assays for screening flavonoid content and DPPH-scavenging activity in sorghum bran and flour","volume":"92","author":"Herald","year":"2012","journal-title":"J. Sci. Food Agric."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1590\/S0100-40422009000600020","article-title":"Antioxidant capacity of eugenol derivatives","volume":"6","author":"Hidalgo","year":"2009","journal-title":"Quim Nova"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/S0957-4166(02)00247-1","article-title":"Enzymatic synthesis of all stereoisomers of 1-phenylpropane-1,2-diol","volume":"13","author":"Kihumbu","year":"2002","journal-title":"Tetrahedron Asymmetry"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1002\/ptr.5812","article-title":"The effect of chosen plant extracts and compounds on mesenchymal stem cells-a bridge between molecular nutrition and regenerative medicine-concise review","volume":"31","author":"Kornicka","year":"2017","journal-title":"Phytother. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.3390\/antibiotics11111500","article-title":"Synergic effect of phthalide lactones and fluconazole and its new analogues as a factor limiting the use of azole drugs against candidiasis","volume":"11","author":"Kr\u0119\u017cel","year":"2022","journal-title":"Antibiotics"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1021\/np50092a006","article-title":"Combination effects of antifungal nagilactones against Candida albicans and two other fungi with phenylpropanoids","volume":"56","author":"Kubo","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.1002\/bit.24857","article-title":"Biochemical characterization of an alcohol dehydrogenase from Ralstonia sp","volume":"110","author":"Kulig","year":"2013","journal-title":"Biotechnol. Bioeng."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.molcatb.2008.08.009","article-title":"Asymmetric synthesis of chiral 2-hydroxy ketones by coupled biocatalytic alkene oxidation and C-C bond formation","volume":"61","author":"Kurlemann","year":"2009","journal-title":"J. Mol. Catal. B Enzym."},{"key":"ref22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/978-0-387-46312-4_10","article-title":"Fluorescence anisotropy","volume-title":"Principles of fluorescence spectroscopy","author":"Lakowicz","year":"2006"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"9978","DOI":"10.1038\/s41598-022-13511-8","article-title":"Anethole rich Clausena heptaphylla (ROXB.) Wight & Arn., essential oil pharmacology and genotoxic efficiencies","volume":"12","author":"Lal","year":"2022","journal-title":"Sci. Rep."},{"key":"ref24","first-page":"1479","article-title":"Inhibition of growth by combined treatment with inhibitors of lactate dehydrogenase and either phenformin or inhibitors of 6-phosphofructo-2-kinase\/fructose-2,6-bisphosphatase 3","volume":"36","author":"Lea","year":"2016","journal-title":"Anticancer Res."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"18889","DOI":"10.1021\/ja310054d","article-title":"Chemical plants: high-value molecules from essential oils","volume":"134","author":"Lummiss","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2598","DOI":"10.4067\/S0717-97072014000300015","article-title":"Antioxidant and toxicity activity in vitro of twelve safrole derivatives","volume":"59","author":"Madrid","year":"2014","journal-title":"J. Chil. Chem. Soc."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"610","DOI":"10.17221\/6469-VETMED","article-title":"Adipose stem cell combined with plasma-based implant bone tissue differentiation in vitro and in a horse with a phalanx digitalis distalis fracture: a case report","volume":"57","author":"Marycz","year":"2012","journal-title":"Vet. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s12015-018-9847-4","article-title":"Static magnetic field (SMF) as a regulator of stem cell fate \u2013 new perspectives in regerative medicine arising from an underestimated tool","volume":"14","author":"Marycz","year":"2018","journal-title":"Stem Cells Rev Rep."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"6919","DOI":"10.1002\/ejoc.201701314","article-title":"Oxidation of vicinal diols to \u03b1-hydroxy ketones with H2O2 and a simple manganese catalyst","volume":"2017","author":"Mecozzi","year":"2017","journal-title":"Eur. J. Org. Chem."},{"key":"ref30","first-page":"1319","article-title":"Anethole, a medicinal plant compound, decreases the production of pro-inflammatory TNF-\u03b1 and IL-1\u03b2 in a rat model of LPS-induced periodontitis","volume":"13","author":"Moradi","year":"2014","journal-title":"Iran. J. Pharm. Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"792","DOI":"10.13005\/ojc\/360501","article-title":"2-lodoxybenzoic acid: an oxidant for functional group transformations: (A-review)","volume":"36","author":"Nair","year":"2020","journal-title":"Orient. J. Chem."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/S0278-6915(99)00037-X","article-title":"The FEMA GRAS assessment of trans-anethole used as a flavouring substance","volume":"7","author":"Newberne","year":"1999","journal-title":"Food Chem. Toxicol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"11819","DOI":"10.1021\/acssuschemeng.8b02107","article-title":"Four atom efficient enzyme cascades for all 4-methoxyphenyl-1,2-propanediol isomers including product crystallization targeting high product concentrations and excellent E-factors","volume":"6","author":"Oeggl","year":"2018","journal-title":"Sust. Chem. Eng."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.3390\/life12111795","article-title":"Molecular mechanisms of action of eugenol in cancer: recent trends and advancement","volume":"12","author":"Padhy","year":"2022","journal-title":"Life"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1002\/cbf.3135","article-title":"The use of erythrocyte fragility to assess xenobiotic cytotoxicity","volume":"33","author":"Pagano","year":"2015","journal-title":"Cell Biochem. Funct."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1080\/01635581.2020.1803927","article-title":"Trans-anethole abrogates cell proliferation and induces apoptosis through the mitochondrial-mediated pathway in human osteosarcoma cells","volume":"73","author":"Pandit","year":"2020","journal-title":"Nutr. Cancer"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1016\/j.tetlet.2004.12.073","article-title":"Selective oxidation of benzylic or allylic hydroxyl group of sec-1,1-diols","volume":"46","author":"Peng","year":"2005","journal-title":"Tetrahedron Lett."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2512","DOI":"10.1002\/cctc.201300093","article-title":"Multistep oxidase-lyase reactions: synthesis of optically active 2-hydroxyketones by using biobased aliphatic alcohols","volume":"5","author":"P\u00e9rez-S\u00e1nchez","year":"2013","journal-title":"ChemCatChem"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/9781444320503.ch4","article-title":"Biosynthesis of Phenylpropanoids and related compounds","volume-title":"Annual Plant Reviews Volume 40: Biochemistry of Plant Secondary Metabolism","author":"Petersen","year":"2010"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1007\/s00232-018-0051-x","article-title":"An In Vitro Study of the Effect of Cytotoxic Triorganotin Dimethylaminophenylazobenzoate Complexes on Red Blood Cells","volume":"251","author":"Pruchnik","year":"2018","journal-title":"J. Membr. Biol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1002\/adsc.201300882","article-title":"Oxidative alkene cleavage by chemical and enzymatic methods","volume":"355","author":"Rajagopalan","year":"2013","journal-title":"Adv. Synth. Catal."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"111777","DOI":"10.1016\/j.molliq.2019.111777","article-title":"Encompassment of isoeugenol in 2-hydroxypropyl-\u03b2-cyclodextrin using ultrasonication: characterization, antioxidant and antibacterial activities","volume":"296","author":"Siva","year":"2019","journal-title":"J. Mol. Liq."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"4946","DOI":"10.3390\/molecules25214946","article-title":"Modulation of lipid metabolism by trans-anethole in hepatocytes","volume":"25","author":"Song","year":"2020","journal-title":"Molecules"},{"key":"ref44","first-page":"2265","article-title":"Anti-hepatoma effect of safrole from Cinnamommum longepaniculatum leaf essential oil in vitro","volume":"7","author":"Song","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1039\/D1RE00173F","article-title":"Chemo-enzymatic oxidative cleavage of isosafrole for the synthesis of piperonal","volume":"6","author":"Tentori","year":"2021","journal-title":"React. Chem. Eng."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3411","DOI":"10.3390\/molecules14093411","article-title":"Fast and green microwave-assisted conversion of essential oil allylbenzenes into the corresponding aldehydes via alkene isomerization and subsequent potassium permanganate promoted oxidative alkene group cleavage","volume":"14","author":"Thi Luu","year":"2009","journal-title":"Molecules"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/biom10121594","article-title":"Antiproliferative, antimicrobial and antiviral activity of \u03b2-aryl-\u03b4-iodo-\u03b3-lactones, their effect on cellular oxidative stress markers and biological membranes","volume":"10","author":"W\u0142och","year":"2020","journal-title":"Biomol. Ther."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.canlet.2004.11.018","article-title":"Eugenol isolated from the essential oil of Eugenia caryophyllata induces a reactive oxygen species-mediated apoptosis in HL-60 human promyelocytic leukemia cells","volume":"225","author":"Yoo","year":"2005","journal-title":"Cancer Lett."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1223123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T06:41:15Z","timestamp":1687761675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1223123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":48,"alternative-id":["10.3389\/fmicb.2023.1223123"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1223123","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,26]]},"article-number":"1223123"}}