Structure-Activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating mycobacterium tuberculosis

Annamaria Lilienkampf, Mao Jialin, Wan Baojie, Wang Yuehong, Scott G. Franzblau, Alan P. Kozikowski

Research output: Contribution to journalArticle

Abstract

Tuberculosis (TB) remains as a global pandemic that is aggravated by a lack of health care, the spread of HIV, and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDRTB) strains. New anti-TB drugs are urgently required to shorten the long 6-12 month treatment regimen and to battle drug-resistant Mtb strains. We have identified several potent quinoline-based anti-TB compounds, bearing an isoxazole containing side-chain. The most potent compounds, 7g and 13, exhibited submicromolar activity against the replicating bacteria (R-TB), with minimum inhibitory concentrations (MICs) of 0.77 and 0.95 μM, respectively. In general, these compounds also had micromolar activity against the nonreplicating persistent bacteria (NRP-TB) and did not show toxicity on Vero cells up to 128 μM concentration. Compounds 7g and 13 were shown to retain their anti-TB activity against rifampin, isoniazid, and streptomycin resistant Mtb strains. The results suggest that quinoline-isoxazole-based anti-TB compounds are promising leads for new TB drug development.

Original languageEnglish (US)
Pages (from-to)2109-2118
Number of pages10
JournalJournal of medicinal chemistry
Volume52
Issue number7
DOIs
StatePublished - Apr 9 2009

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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