Design, synthesis and biological evaluation of potential antibacterial butyrolactones.
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 9.38μg/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 C4position had an important influence on the antibacterial activity. An optimum length of the alkyl chain at the C5position 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 C4position indicating the important dual role contributed by these two substituents which might be involved in their mechanism of action.
Equipe Microbiologie Risques Infectieux, EA 1254, SFR Biosit, Université Bretagne Loire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Laboratory of Microbiology, Department of Biology, Faculty of Sciences I, Lebanese University, Hadath Campus, Beirut, Lebanon.
Alaa
A
Sweidan
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.
Marylene
M
Chollet-Krugler
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.
Pierre
P
van de Weghe
Laboratory of Microbiology, Department of Biology, Faculty of Sciences I, Lebanese University, Hadath Campus, Beirut, Lebanon.
Ali
A
Chokr
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.
Sophie
S
Tomasi
Equipe Microbiologie Risques Infectieux, EA 1254, SFR Biosit, Université Bretagne Loire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Martine
M
Bonnaure-Mallet
Equipe Microbiologie Risques Infectieux, EA 1254, SFR Biosit, Université Bretagne Loire, Université de Rennes 1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Latifa
L
Bousarghin
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D054773:Streptococcus gordonii / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D007783:Lactones
Antibacterial; Butyrolactones; Cytotoxicity; Lichen; Streptococcus gordonii