Design, synthesis, and pharmacological evaluation of mefloquine-based ligands as novel antituberculosis agents

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

Research output: Contribution to journalArticle


Tuberculosis (TB) is presently regarded as one of the most dangerous infective diseases worldwide and one of the major AIDS-associated infections. To shorten the current treatment regimen, there is an urgent need to identify new anti-TB agents which are active against both replicating TB (R-TB) and nonreplicating TB (NRP-TB). Mefloquine, a well-known antimalarial drug was found to possess reasonable activity against NRP-TB, and accordingly, 30 new analogues were synthesized and evaluated for their anti-TB activity against Mycobacterium tuberculosis H37Rv. As the target of mefloquine in Mycobacterium tuberculosis remains unknown, we resorted to modifying mefloquine in a variety of chemically convenient ways, which led us in turn to the active hydrazone 10a. Further modifications of 10a led to compound 7 f, with an improved anti-TB activity/selectivity profile with both less cytotoxicity and less predicted CNS side effects compared with mefloquine. The clear structure-activity relationships (SARs) derived from this study should facilitate our ultimate goal of identifying improved anti-TB agents.

Original languageEnglish (US)
Pages (from-to)1624-1630
Number of pages7
Issue number11
StatePublished - Nov 12 2007



  • Hydrazones
  • Ligand-based drug design
  • Mefloquine
  • Structure-activity relationships
  • Tuberculosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry

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