Design,synthesis and biological evaluation of potential antibacterial butyrolactones |
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| Institution: | 1. Equipe Microbiologie Risques Infectieux, EA 1254, SFR Biosit, Université Bretagne Loire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France;2. UMR CNRS 6226, Institut des Sciences Chimiques de Rennes, Equipe PNSCM, Université Bretagne Loire, Université de Rennes 1, 2 Avenue du Pr. Léon Bernard, F-35043 Rennes, France;3. Laboratory of Microbiology, Department of Biology, Faculty of Sciences I, Lebanese University, Hadath Campus, Beirut, Lebanon;1. Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;2. Solid State Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;3. Process Development Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India;3. Interdisciplinary Stem Cell Institute (ISCI), University of Miami Miller School of Medicine, Miami, Florida 33136;4. Department of Cardiology, Gulhane Military Medical Academy, Haydarpasa Hospital, 34668 Istanbul, Turkey;5. Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287;6. Departamento de Ciencias Basicas Biomedicas, Facultad de Ciencias de la Salud, Universidad de Talca, 3460000 Talca, Chile;1. Laboratory of Pharmaceutical Technology and Biopharmacy, Department of Pharmacy, Centre Interfacultaire de Recherche du Médicament (CIRM), University of Liege, 4000 Liège, Belgium;2. Laboratory of Medicinal Chemistry, Department of Pharmacy, Centre Interfacultaire de Recherche du Médicament (CIRM), University of Liege, 4000 Liège, Belgium;1. From the Richardson Centre for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.;1. Department of Organic Chemistry, College of Chemistry, Jilin University, Changchun 130012, PR China;2. Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi’an 710069, PR China;1. ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Chemistry, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia;2. School of Biological Sciences, Department of Molecular and Cellular Biology, The University of Adelaide, North Terrace, Adelaide, SA 5005, Australia |
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| Abstract: | Novel butyrolactone analogues were designed and synthesized based on the known lichen antibacterial compounds, lichesterinic acids (B-10 and B-11), by substituting different functional groups on the butyrolactone ring trying to enhance its activity. All synthesized butyrolactone analogues were evaluated for their in vitro antibacterial activity against Streptococcus gordonii. Among the derivatives, B-12 and B-13 had the lowest MIC of 9.38 μg/mL where they have shown to be stronger bactericidals, by 2–3 times, than the reference antibiotic, doxycycline. These two compounds were then checked for their cytotoxicity against human gingival epithelial cell lines, Ca9–22, and macrophages, THP-1, by MTT and LDH assays which confirmed their safety against the tested cell lines. A preliminary study of the structure–activity relationships unveiled that the functional groups at the C4 position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C5 position registered the best antibacterial inhibitory activity however as its length increased the bactericidal effect increased as well. This efficiency was attained by a carboxyl group substitution at the C4 position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action. |
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| Keywords: | Lichen Butyrolactones Antibacterial Cytotoxicity |
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