Synthesis and in vitro evaluation of the antitubercular and antibacterial activity of novel oxazolidinones bearing octahydrocyclopenta[c]pyrrol-2-yl moieties

Deepak Bhattarai, Ju Hyeon Lee, Seon Hee Seo, Ghilsoo Nam, Hyunah Choo, Soon Bang Kang, Jin Hwan Kwak, Taegwon Oh, Sang Nae Cho, Ae Nim Pae, Eunice Eunkyeong Kim, Nakcheol Jeong, Gyochang Keum

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4 Citations (Scopus)

Abstract

A novel series of oxazolidinone-class antimicrobial agents with 5-substituted octahydrocyclopenta[c]-pyrrole moieties at the C-ring of linezolid and an acetamide or 1,2,3-triazole ring as the C-5 side chain of the oxazolidinone ring were prepared. The resulting series of compounds were evaluated for in vitro antimicrobial activity against Mycobacterium tuberculosis and a panel of clinically important resistant Gram-positive and -negative bacteria. Among them, endo-alcohol 2a and exo-alcohol 2b showed potent inhibitory activity against M. tuberculosis H37Rv, which was superior to that of linezolid. Several analogues in this series showed potent in vitro antibacterial activity against the clinically important vancomycin-resistant bacteria and showed similar or better potency against linezolid-resistant methicillin-resistant Staphylococcus aureus (MRSA) strains. The hydroxyl group in the azabicyclic C-ring interacted with the same hydrophobic pocket as linezolid based on a docking study. Selected compounds with high antimicrobial activity showed good human microsomal stability and low CYP isozyme and monoamine oxidase (MAO) inhibition.

Original languageEnglish
Pages (from-to)1214-1224
Number of pages11
JournalChemical and Pharmaceutical Bulletin
Volume62
Issue number12
DOIs
Publication statusPublished - 2014 Dec 1

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

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    Bhattarai, D., Lee, J. H., Seo, S. H., Nam, G., Choo, H., Kang, S. B., Kwak, J. H., Oh, T., Cho, S. N., Pae, A. N., Kim, E. E., Jeong, N., & Keum, G. (2014). Synthesis and in vitro evaluation of the antitubercular and antibacterial activity of novel oxazolidinones bearing octahydrocyclopenta[c]pyrrol-2-yl moieties. Chemical and Pharmaceutical Bulletin, 62(12), 1214-1224. https://doi.org/10.1248/cpb.c14-00510