Synthesis and evaluation of nitrofuranyl methyl N-heterocycles derivatives as novel antitubercular agents

Future Med Chem. 2018 Sep 1;10(17):2059-2068. doi: 10.4155/fmc-2018-0112. Epub 2018 Jul 11.

Abstract

Aim: Tuberculosis (TB) is one of the world's deadliest chronic infectious diseases caused mainly by Mycobacterium tuberculosis (MTB). Many nitrofuran derivatives were found to possess promising anti-TB potential and have been widely studied. In our previous study, we discovered diazaspiro-nitrofuran IMB1701-1702 as potent anti-TB agents.

Methodology: We report herein a series of nitrofuranyl methyl N-heterocycles based on IMB1701-1702. Results reveal that most of them show potent activity (minimum inhibitory concentration: <0.016-0.062 μg/ml) against MTB H37Rv strain. Especially, compound 7h without cytotoxicity, has the same minimum inhibitory concentration value of ≤0.016 μg/ml as PBTZ169 against both MTB H37Rv strain and two clinically isolated multidrug-resistant MTB strains.

Conclusion: The newly designed compound 7h might be a promising anti-TB candidate.

Keywords: MDR-MTB; MTB H37Rv; antitubercular; nitrofuranyl; structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / chemical synthesis
  • Antitubercular Agents / chemistry*
  • Antitubercular Agents / pharmacology*
  • Chlorocebus aethiops
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Nitrofurans / chemical synthesis
  • Nitrofurans / chemistry*
  • Nitrofurans / pharmacology*
  • Structure-Activity Relationship
  • Tuberculosis / drug therapy
  • Vero Cells

Substances

  • Antitubercular Agents
  • Nitrofurans