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The main goal of the current study was to evaluate the influence of 4\u2010substituted piperazine moieties at position 7 of the \u03b2\u2010thujaplicin scaffold, on the antimicrobial activity. In order to determine the biological activity of the \u03b2\u2010thujaplicin derivatives, a microdilution method was used against a wide variety of bacteria and fungi. <jats:italic>Pseudomonas aeruginosa<\/jats:italic> PAO 1 was used for testing antiquorum and antibiofilm effects. Four human tumor cell lines (MCF\u20107, NCI\u2010H460, HeLa, and HepG2) and a porcine liver derived cell line (PLP2) were used for testing antitumor and cytotoxic activity. The compounds present better antibacterial and antifungal activity in comparison with approved antimicrobials used as control agents. \u03b2\u2010Thujaplicin showed strong antibacterial and antifungal activities against all tested species. Further studies of their antibacterial activity revealed that all compounds presented good antibiofilm and antiquorum effects. Fungi were more susceptible than bacteria to the tested compounds, with the exception of MK150, which possessed the best antibacterial effect. None of the tested compounds, at the GI<jats:sub>50<\/jats:sub> values obtained for the tumor cell lines, have shown toxicity for non\u2010tumor liver cells (PLP2). The prediction of physicochemical properties of the compounds was performed to further explain the structure\u2013activity relationship. Finally, in order to explore a possible mechanism of action of the synthesized compounds, molecular docking studies were performed on CYP51 (14\u2010a lanosterol demethylase), an important component of the fungal cell membrane.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ardp.201600095","type":"journal-article","created":{"date-parts":[[2016,7,12]],"date-time":"2016-07-12T09:25:09Z","timestamp":1468315509000},"page":"698-709","source":"Crossref","is-referenced-by-count":16,"title":["Antimicrobial\/Antibiofilm Activity and Cytotoxic Studies of \u03b2\u2010Thujaplicin Derivatives"],"prefix":"10.1002","volume":"349","author":[{"given":"Theano","family":"Fotopoulou","sequence":"first","affiliation":[{"name":"Institute of Biology, Medicinal Chemistry and Biotechnology National Hellenic Research Foundation Athens Greece"}]},{"given":"Ana","family":"\u0106iri\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d University of Belgrade Belgrade Serbia"}]},{"given":"Eftichia","family":"Kritsi","sequence":"additional","affiliation":[{"name":"Institute of Biology, Medicinal Chemistry and Biotechnology National Hellenic Research Foundation Athens Greece"}]},{"given":"Ricardo C.","family":"Calhelha","sequence":"additional","affiliation":[{"name":"Mountain Research Centre (CIMO, ESA) Polytechnic Institute of Bragan\u00e7a Bragan\u00e7a Portugal"}]},{"given":"Isabel C.F.R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Mountain Research Centre (CIMO, ESA) Polytechnic Institute of Bragan\u00e7a Bragan\u00e7a Portugal"}]},{"given":"Marina","family":"Sokovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d University of Belgrade Belgrade Serbia"}]},{"given":"Panagiotis","family":"Zoumpoulakis","sequence":"additional","affiliation":[{"name":"Institute of Biology, Medicinal Chemistry and Biotechnology National Hellenic Research Foundation Athens Greece"}]},{"given":"Maria","family":"Koufaki","sequence":"additional","affiliation":[{"name":"Institute of Biology, Medicinal Chemistry and Biotechnology National Hellenic Research Foundation Athens Greece"}]}],"member":"311","published-online":{"date-parts":[[2016,7,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2478\/johr-2014-0001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ps.379"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.23.995"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg037"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2012.12.007"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00078.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2009.05.038"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.11.011"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01543-08"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.02.027"},{"key":"e_1_2_7_12_1","author":"Jayakumar T.","year":"2013","journal-title":"Evid. 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