Design, synthesis, and biological evaluation of novel imidazo[1,2-a]pyridinecarboxamides as potent anti-tuberculosis agents

Oluseye K. Onajole, Shichun Lun, Young Ju Yun, Damkam Y. Langue, Michelle Jaskula-Dybka, Adrian Flores, Eriel Frazier, Ashle C. Scurry, Ambernice Zavala, Karen R. Arreola, Bryce Pierzchalski, A. Jean Luc Ayitou, William R. Bishai

Research output: Contribution to journalLetterpeer-review

Abstract

Tuberculosis (TB) is a highly infectious disease that has been plaguing the human race for centuries. The emergence of multidrug-resistant strains of TB has been detrimental to the fight against tuberculosis with very few safe therapeutic options available. As part of an ongoing effort to identify potent anti-tuberculosis agents, we synthesized and screened a series of novel imidazo[1,2-a]pyridinecarboxamide derivatives for their anti-tuberculosis properties. These compounds were designed based on reported anti-tuberculosis properties of the indolecarboxamides (I2Cs) and imidazo[1,2-a]pyridinecarboxamides (IPAs). In this series, we identified compounds 15 and 16 with excellent anti-TB activity against H37Rv strain of tuberculosis (MIC = 0.10–0.19 μM); these compounds were further screened against selected clinical isolates of Mtb. Compounds 15 and 16 showed excellent activities against multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB (MIC range: 0.05–1.5 μM) with excellent selectivity indices. In addition, preliminary ADME studies on compound 16 showed favorable pharmacokinetic properties.

Original languageEnglish (US)
Pages (from-to)1362-1371
Number of pages10
JournalChemical Biology and Drug Design
Volume96
Issue number6
DOIs
StatePublished - Dec 2020

Keywords

  • Imidazo[1,2-apyridine-3-carboxamide
  • Indole-2-carboxamide
  • antituberculosis activity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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