Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents

• An analogous library of 2-substituted quinolines has been synthesized.
• Compounds were assessed for antileishmanial potential and metabolic stability.
• The most potent compound 26g showed promising in vitro and in vivo activity.
• The salt form of 26g showed 84% inhibition at 50 mg/kg × 5d, p.o. in hamster model.
• PK data of compound 26g indicating that the compound is well distributed.

An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in vitro and in vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be the most active; exhibited an IC50 value of 0.2 μM and >180 fold selectivity. The hydrochloride salt of (26g) showed 84.26 ± 4.44 percent inhibition at 50 mg/kg × 5 days (twice daily, oral route) dose in L. donovani/hamster model. The efficacy was well correlated with the PK data observed which indicating that the compound is well distributed.

A library of 2-substituted quinoline compounds was synthesized and screened for their antileishmanial potential. Compound (26g) was found most promising and the efficacy was correlated with the PK data observed.Figure optionsDownload as PowerPoint slide