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Current Microbiology

, Volume 57, Issue 5, pp 463–468 | Cite as

Identification of a Potential Lead Structure for Designing New Antimicrobials to Treat Infections Caused by Staphylococcus epidermidis-Resistant Strains

  • Luiz C. S. Pinheiro
  • Paula A. Abreu
  • Ilidio F. Afonso
  • Bruno Leal
  • Luiz C. D. Corrêa
  • Júlio C. Borges
  • Isakelly P. Marques
  • André L. Lourenço
  • Plinio Sathler
  • Andre L. dos Santos
  • Cid A. Medeiros
  • Lúcio M. Cabral
  • Maurício L. O. Júnior
  • Gilberto A. Romeiro
  • Vitor F. Ferreira
  • Carlos R. Rodrigues
  • Helena C. CastroEmail author
  • Alice M. R. BernardinoEmail author
Article

Abstract

Bacterial infections are a significant cause of morbidity and mortality among critically ill patients. The increase of antibiotic resistance in bacteria from human microbiota—such as Staphylococcus epidermidis, an important nosocomial pathogen that affects immunocompromised patients or those with indwelling devices—increased the desire for new antibiotics. In this study we designed, synthesized, and determined the antimicrobial activity of 27 thieno[2,3-b]pyridines (1, 2, 2a–2m, 3, 3a–3m) derivatives against a drug-resistant clinical S. epidermidis strain. In addition, we performed a structure-activity relationship analysis using a molecular modeling approach, and discuss the drug absorption, distribution, metabolism, excretion, and toxicity profile and Lipinski’s “rule of five,” which are tools to assess the relationship between structures and drug-like properties of active compounds. Our results showed that compound 3b (5-(1H-tetrazol-5-yl)-4-(3`-methylphenylamino)thieno[2,3-b]pyridine) was as active as oxacillin and chloramphenicol but with lower theoretical toxicity risks and a better drug likeness and drug score potential than chloramphenicol. All molecular modeling and biological results reinforced the promising profile of 3b for further experimental investigation and development of new antibacterial drugs.

Keywords

Oxacillin Drug Score Pyridine Derivative Meta Position Phenylamino 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal Docente (CAPES), and Programa de Pós-Graduação da Universidade Federal Fluminense (UFF) for the financial support and H.C.C., P.S., and A.L.L. fellowships.

Supplementary material

284_2008_9234_MOESM1_ESM.doc (40 kb)
MOESM1 [INSERT CAPTION HERE] (DOC 39 kb)

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Luiz C. S. Pinheiro
    • 1
  • Paula A. Abreu
    • 2
  • Ilidio F. Afonso
    • 3
  • Bruno Leal
    • 2
  • Luiz C. D. Corrêa
    • 2
  • Júlio C. Borges
    • 1
  • Isakelly P. Marques
    • 1
  • André L. Lourenço
    • 2
  • Plinio Sathler
    • 2
  • Andre L. dos Santos
    • 2
  • Cid A. Medeiros
    • 2
  • Lúcio M. Cabral
    • 3
  • Maurício L. O. Júnior
    • 2
  • Gilberto A. Romeiro
    • 1
  • Vitor F. Ferreira
    • 1
  • Carlos R. Rodrigues
    • 3
  • Helena C. Castro
    • 2
    Email author
  • Alice M. R. Bernardino
    • 1
    Email author
  1. 1.Instituto de Química, Departamento de Química Orgânica, Programa de Pós-Graduação em Química OrgânicaUniversidade Federal FluminenseNiteroiBrazil
  2. 2.Instituto de Biologia, Departamento de Biologia Celular e Molecular, LABioMolUniversidade Federal FluminenseNiteroiBrazil
  3. 3.ModMolQSAR, Faculdade de FarmáciaUniversidade Federal do Rio de JaneiroRio de JaneiroBrazil

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