title: Searching for a potential antibacterial lead structure against bacterial biofilms among new naphthoquinone compounds.
abstract: OBJECTIVE
  The aims of this study were to design, synthesize and to evaluate 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones against Gram-negative and Gram-positive bacterial strains, including methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, to probe for potential lead structures.
  
  
  RESULTS
  Thirty-six new analogues were prepared with good yields using a simple, fast, operational three-procedure reaction and a thiol addition to an ο-quinone methide using microwave irradiation. All compounds were tested against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 15290, Serratia marcescens ATCC 14756, Klebsiella pneumoniae ATCC 4352, Enterobacter cloacae ATCC 23355, Enterococcus faecalis ATCC 29212, S. aureus ATCC 25923, Staphylococcus simulans ATCC 27851, Staphylococcus epidermidis ATCC 12228 and a hospital strain of MRSA. Their antibacterial activity was determined using the disc diffusion method, revealing the activity of 19 compounds, mainly against Gram-positive strains. Interestingly, the minimal inhibitory concentration ranges detected for the hit molecules (32-128 μg ml-1) were within Clinical and Laboratory Standards Institute levels. Promisingly, compound 15 affected the MRSA strain, with a reduction of up to 50% in biofilm formation, which is better than vancomycin as biofilm forms a barrier against the antibiotic that avoids its action.
  
  
  CONCLUSIONS
  After probing 36 naphthoquinones for a potential antibacterial lead structure against the bacterial biofilm, we found that compound 15 should be explored further and also should be structurally modified in the near future to test against Gram-negative strains.
  
  
  CONCLUSIONS
  Since vancomycin is one of the last treatment options currently available, and it is unable to inhibit biofilm, the research of new antimicrobials is urgent. In this context, 2-hydroxy-3-phenylsulfanylmethyl-[1,4]-naphthoquinones proved to be a promising lead structure against MRSA and bacterial biofilm.
authors.affiliation: Organic Chemistry Department, Chemistry Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: C S
authors.initials: CS
authors.lastname: Moreira
authors.affiliation: Molecular and Cell Biology Department, PPBI, Biology Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: A C J A
authors.initials: AC
authors.lastname: Silva
authors.affiliation: Molecular and Cell Biology Department, PPBI, Biology Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: J S
authors.initials: JS
authors.lastname: Novais
authors.affiliation: Department of Medical Microbiology, Institute of Microbiology Professor Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Sá Figueiredo
authors.affiliation: Organic Chemistry Department, Chemistry Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: V F
authors.initials: VF
authors.lastname: Ferreira
authors.affiliation: Organic Chemistry Department, Chemistry Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: D R
authors.initials: DR
authors.lastname: da Rocha
authors.affiliation: Molecular and Cell Biology Department, PPBI, Biology Institute, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil.
authors.forename: H C
authors.initials: HC
authors.lastname: Castro
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D016972:Enterobacter cloacae; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology*; D011513:Proteus mirabilis / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects; D014640:Vancomycin
chemical_list: D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; D014640:Vancomycin
keywords: Escherichia coli (all potentially pathogenic types); antimicrobials; biofilms; resistance; staphylococci