In vivo studies of the effect of PPQ-6, a quinoline-based agent against Schistosoma mansoni in mice

Exp Parasitol. 2020 Aug:215:107933. doi: 10.1016/j.exppara.2020.107933. Epub 2020 Jun 7.

Abstract

Schistosomiasis is still a public health problem. Praziquantel is the only drug available for treatment of all forms of human schistosomiasis. Although praziquantel is an effective drug against all species of human schistosomes, concerns about resistance have been raised, especially in endemic areas. A hybrid compound containing several pharmacophore within a single molecule is a promising strategy. Here, we described the anti-schistosomal effect of 4-(2-Chloroquinolin-3-yl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile (PPQ-6), a hybrid drug based on quinoline and pyridine. PPQ-6 was given as two regimens (20 or 40 mg/kg). In both regimens, PPQ-6 significantly reduced liver and spleen indices, nitric oxide production, tissue egg load, hepatic granuloma size and count, immature eggs and total worm burden especially females. Our findings suggested that PPQ-6 is a promising anti-schistosomal agent; however more research is needed to elucidate its mechanism of action and report its activity on juvenile schistosomes and other species of human schistosomes.

Keywords: Granuloma; Hemozoin; PPQ-6; Quinoline; Schistosoma mansoni.

MeSH terms

  • Analysis of Variance
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Liver / parasitology
  • Liver / pathology
  • Male
  • Mice
  • Nitric Oxide / analysis
  • Pyridines / chemistry
  • Pyridines / pharmacology*
  • Pyridines / therapeutic use
  • Quinolines / chemistry
  • Quinolines / pharmacology*
  • Quinolines / therapeutic use
  • Random Allocation
  • Schistosoma mansoni / drug effects*
  • Schistosomiasis mansoni / drug therapy*
  • Schistosomicides / chemistry
  • Schistosomicides / pharmacology*
  • Schistosomicides / therapeutic use
  • Sex Factors
  • Spleen / parasitology
  • Spleen / pathology

Substances

  • Pyridines
  • Quinolines
  • Schistosomicides
  • Nitric Oxide