Design and Synthesis of 2-Arylbenzimidazoles and Evaluation of Their Inhibitory Effect against Chlamydia pneumoniae

Leena Keurulainen, Olli Salin, Antti Siiskonen, Jan Marco Kern, Joni Alvesalo, Paula Kiuru, Matthias Maass, Jari Yli-Kauhaluoma, Pia Vuorela

Research output: Contribution to journalArticleScientificpeer-review

37 Citations (Scopus)

Abstract

Chlamydia pneumoniae is an intracellular bacterium that responds poorly to antibiotic treatment. Insufficient antibiotic usage leads to chronic infection, which is linked to disease processes of asthma, atherosclerosis, and Alzheimer's disease. The Chlamydia research lacks genetic tools exploited by other antimicrobial research, and thus other approaches to drug discovery must be applied. A set of 2-arylbenzimidazoles was designed based on our earlier findings, and 33 derivatives were synthesized. Derivatives were assayed against C. pneumoniae strain CWL-029 in an acute infection model using TR-FIA method at a concentration of 10 mu M, and the effects of the derivatives on the host cell viability were evaluated at the same concentration. Fourteen compounds showed at least 80% inhibition, with only minor changes in host cell viability. Nine most potential compounds were evaluated using immunofluorescence microscopy on two different strains of C. pneumoniae CWL-029 and CV-6. The N-[3-(1H-benzimidazol-2-yl)phenyl]-3-methylbenzamide (42) had minimal inhibitory concentration (MIC) of 10 mu M against CWL-029 and 6.3 mu M against the clinical strain CV-6. This study shows the high antichlamydial potential of 2-arylbenzimidazoles, which also seem to have good characteristics for lead compounds.

Original languageEnglish
Pages (from-to)7664-7674
Number of pages11
JournalJOURNAL OF MEDICINAL CHEMISTRY
Volume53
Issue number21
DOIs
Publication statusPublished - 11 Nov 2010
Externally publishedYes
Publication typeA1 Journal article-refereed

Keywords

  • FOAM CELL-FORMATION
  • IN-VITRO
  • C57BL/6J MICE
  • BENZIMIDAZOLE DERIVATIVES
  • CHLAMYDOPHILA-PNEUMONIAE
  • SEROLOGICAL EVIDENCE
  • STRAIN TWAR
  • INFECTION
  • TRACHOMATIS
  • ATHEROSCLEROSIS

Cite this