{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:35:41Z","timestamp":1778686541044,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T00:00:00Z","timestamp":1647907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104797\/Z\/14\/Z."],"award-info":[{"award-number":["104797\/Z\/14\/Z."]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000947","name":"Australian Cancer Research Foundation","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100000947","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ramaciotti Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Five focused compound libraries (forty-nine compounds), based on prior studies in our laboratory were synthesized and screened for antibiotic and anti-fungal activity against S.\u00a0aureus, E.\u00a0coli, K.\u00a0pneumoniae, P. aeruginosa, A. baumannii,\u00a0C. albicans and C. neoformans. Low levels of activity, at the initial screening concentration of 32 \u03bcg\/mL, were noted with analogues of (Z)-2-(3,4-dichlorophenyl)-3-phenylacrylonitriles which made up the first two focused libraries produced. The most promising analogues possessing additional substituents on the terminal aromatic ring of the synthesised acrylonitriles. Modifications of the terminal aromatic moiety were explored through epoxide installation flowed by flow chemistry mediated ring opening aminolysis with discreet sets of amines to the corresponding amino alcohols. Three new focused libraries were developed from substituted anilines, cyclic amines, and phenyl linked heterocyclic amines. The aniline-based compounds were inactive against the bacterial and fungal lines screened. The introduction of a cyclic, such as piperidine, piperazine, or morpholine, showed &gt;50% inhibition when evaluated at 32 \u03bcg\/mL compound concentration against methicillin-resistant Staphylococcus\u00a0aureus. Examination of the terminal aromatic substituent via oxirane aminolysis allowed for the synthesis of three new focused libraries of afforded amino alcohols. Aromatic substituted piperidine or piperazine switched library activity from antibacterial to anti-fungal activity with ((Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(4-methylpiperazin-1-yl)propoxy)phenyl)acrylonitrile), ((Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(4-(4-hydroxyphenyl)piperazin-1-yl)propoxy)-phenyl)acrylonitrile) and ((Z)-3-(4-(3-(4-cyclohexylpiperazin-1-yl)-2-hydroxypropoxy)-phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile) showing &gt;95% inhibition of Cryptococcus neoformans var. grubii\u00a0H99 growth at 32 \u03bcg\/mL. While (Z)-3-(4-(3-(cyclohexylamino)-2-hydroxypropoxy)phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile, (S,Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(piperidin-1-yl)propoxy)phenyl)acrylonitrile, (R,Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(piperidin-1-yl)propoxy)phenyl)acrylonitrile, (Z)-2-(3,4-dichlorophenyl)-3-(4-(2-hydroxy-3-(D-11-piperidin-1-yl)propoxy)phenyl)-acrylonitrile, and (Z)-3-(4-(3-(4-cyclohexylpiperazin-1-yl)-2-hydroxypropoxy)-phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile 32 \u03bcg\/mL against Staphylococcus\u00a0aureus.<\/jats:p>","DOI":"10.3390\/molecules27072050","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T23:30:23Z","timestamp":1647991823000},"page":"2050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Amino Alcohols as Potential Antibiotic and Antifungal Leads"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9560-301X","authenticated-orcid":false,"given":"Jennifer R.","family":"Baker","sequence":"first","affiliation":[{"name":"Chemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive Callaghan, Newcastle, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J.","family":"Cossar","sequence":"additional","affiliation":[{"name":"Chemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive Callaghan, Newcastle, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-2292","authenticated-orcid":false,"given":"Mark A. T.","family":"Blaskovich","sequence":"additional","affiliation":[{"name":"Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-0484","authenticated-orcid":false,"given":"Alysha G.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Zuegg","sequence":"additional","affiliation":[{"name":"Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Community for Open Antimicrobial Drug Discovery, Centre for Superbug Solutions, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-062X","authenticated-orcid":false,"given":"Peter J.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Biology, School of Environmental & Life Sciences, The University of Newcastle, University Drive Callaghan, Newcastle, NSW 2308, Australia"},{"name":"Molecular Horizons, School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, NSW 2522, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7125-863X","authenticated-orcid":false,"given":"Adam","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Chemistry, School of Environmental & Life Sciences, The University of Newcastle, University Drive Callaghan, Newcastle, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","article-title":"Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study","volume":"16","author":"Liu","year":"2016","journal-title":"Lancet Infect. 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