Synthesis, characterization and pharmacological screening of some novel 5-imidazopyrazole incorporated polyhydroquinoline derivatives

Eur J Med Chem. 2014 May 6:78:207-16. doi: 10.1016/j.ejmech.2014.02.015. Epub 2014 Mar 19.

Abstract

A new category of polyhydroquinoline derivatives 8a-t were synthesized in moderate to good yield (64-85%) by one-pot three-component cyclocondensation reaction of 5-(1H-imidazol-1-yl)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde 3 with various enaminones 6a-h and different active methylene compounds (malononitrile 7a, ethylcaynoacetate 7b and caynoacetamide 7c) in absolute ethanol. The newly synthesized compounds were evaluated for their in vitro antimalarial activity against Plasmodium falciparum, in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi and also for their antitubercular activity against Mycobacterium tuberculosis H37Rv strain. Two of them (8n, 8t) exhibited excellent antimalarial activity. Some of them exhibited excellent antibacterial activity and moderate antituberculosis activity compared with the first line drugs.

Keywords: 5-Imidazopyrazole incorporated polyhydroquinolines; Antimalarial activity; Antimicrobial activity; Antituberculosis activity; Multicomponent reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Bacteria / drug effects
  • Dose-Response Relationship, Drug
  • Fungi / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Polymers / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Quinolines / chemical synthesis
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antimalarials
  • Polymers
  • Pyrazoles
  • Quinolines
  • imidazopyrazole