%0 Journal Article %T Design, synthesis and biological evaluation of potential antibacterial butyrolactones %+ Faculty of Engineering, Beirut, Lebanon %+ Microbiologie : Risques Infectieux %+ Institut des Sciences Chimiques de Rennes (ISCR) %A Sweidan, A. %A Chollet-Krugler, M. %A Weghe, P., van De %A Chokr, A. %A Tomasi, S. %A Bonnaure-Mallet, M. %A Bousarghin, Latifa %Z FundingThe research was supported by Rennes I University, CNRS (France), Association of Specialization and Scientific Orientation (Liban) and Melanolichen Grant (France).AcknowledgmentsWe acknowledge Prof. J. Boustie (Head of PNSCM team) for his helpful discussion. We would also like to thank C. Le Lann and N. Oliviero (EA 1254—Rennes I university), and Nathalie Legrave (UMR CNRS 6226—Rennes I University) for their technical assistance. %< avec comité de lecture %@ 0968-0896 %J Bioorganic and Medicinal Chemistry %I Elsevier %V 24 %N 22 %P 5823--5833 %8 2016-11 %D 2016 %R 10.1016/j.bmc.2016.09.040 %M 27687969 %K Antibacterial %K Butyrolactones %K Cytotoxicity %K Lichen %K Streptococcus gordonii %Z Chemical SciencesJournal articles %X 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. © 2016 Elsevier Ltd %G English %2 https://univ-rennes.hal.science/hal-01398051/document %2 https://univ-rennes.hal.science/hal-01398051/file/Sweidan%20et%20al.%20-%20Design%2C%20Synthesis%20and%20Biological%20Evaluation%20of%20Pot.pdf %L hal-01398051 %U https://univ-rennes.hal.science/hal-01398051 %~ UNIV-RENNES1 %~ CNRS %~ INSA-RENNES %~ ENSC-RENNES %~ IFR140 %~ ISCR %~ MRI %~ SCR-PNSCM %~ STATS-UR1 %~ NUMECAN %~ UR1-SPM %~ INC-CNRS %~ NUMECAN-CIMIAD %~ UR1-UFR-SVE %~ UR1-UFR-SPM %~ UR1-HAL %~ ISCR-CORINT %~ UR1-SDLM %~ UR1-SDV %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ INSA-GROUPE %~ ISCR-CORINT2 %~ NUMECAN-METHER %~ UR1-MMS %~ UR1-BIO-SA %~ ISCR-CORINT3 %~ TEST2-HALCNRS