γ-Alkylidene-γ-lactones and isobutylpyrrol-2(5H)-ones analogues to rubrolides as inhibitors of biofilm formation by gram-positive and gram-negative bacteria.
Several molecules have been discovered that interfere with formation of bacterial biofilms, opening a new strategy for the development of more efficient treatments in case of antibiotic resistant bacteria. Amongst the most active compounds are some natural brominated furanones from marine algae Delisea pulchra that have proven to be able to control pathogenic biofilms. We have recently reported that some rubrolide analogues are able to inhibit biofilm formation of Enterococcus faecalis. In the present Letter we describe results of the biological evaluation of a small library of 28 compounds including brominated furanones and the corresponding lactams against biofilm formation of Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus mutans. Our results showed that in general these compounds were more active against biofilms of S. epidermidis and P. aeruginosa, with little or no inhibition of planktonic bacterial growth. In some cases they were able to prevent biofilm formation of P. aeruginosa at concentrations as low as 0.6 μg/mL (1.3 μM, compound 3d) and 0.7 μg/mL (1.3 μM, 3f). Results also indicate that, in general, lactams are more active against biofilms than their precursors, thus designating this class of molecules as good candidates for the development of a new generation of antimicrobial drugs targeted to biofilm inhibition.
Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil.
Ulisses A
UA
Pereira
Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil; Department of Chemistry, Universidade Federal de Minas Gerais, Av. Pres. Antônio Carlos, 6627, Campus Pampulha, CEP 31270-901 Belo Horizonte, MG, Brazil. Electronic address: lcab@ufmg.br.
Luiz C A
LC
Barbosa
Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil.
Célia R A
CR
Maltha
Department of Chemistry, Federal University of Viçosa, Av. PH Rolfs, Viçosa, MG 36570-000, Brazil.
Antônio J
AJ
Demuner
Gene Solutions, LLC, One Boars Head Pointe, Suite 131, Charlottesville, VA 22903, USA.
Mohammed A
MA
Masood
Department of Biologie, University of Cergy Pontoise, 2, Av. Adolphe Chauvin, 95302 Cergy Pontoise, France.
Andréa L
AL
Pimenta
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D013295:Streptococcus mutans / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D005663:Furans; D007783:Lactones; D054852:Small Molecule Libraries
Biofilm inhibition; Lactams; Pseudomonas aeruginosa; Staphylococcus aureus; Staphylococcus epidermidis; Streptococcus mutans