ANTILEISHMANIAL MODE OF ACTION OF DERIVATIVES OF THE QUINOLINE ALKALOID (QUININE) FROM THE BARK OF CINCHONA LEDGERIANA

Quinolones are a group of low-molecular weight, extremely potent antimicrobial agents. The quinolone era is now nearly a quarter of a century old. Quinine was the structural model for the design of the 7-chloro-4-aminoquinoline and 8-aminoquinoline classes of synthetic antimalarials.

Leishmania spp. share many common biochemical characteristics with malarial organisms and it is for that reason we investigated the antileishmanial properties of the antimalarial quinolone derivatives.

The antimalarial 8-aminoquinoline, WR242511, demonstrated strong inhibition to the growth of leishmanial cells in vitro. Its IC50 (concentration at 50% inhibition) was 2.5 μM against L. mexicana 227. The mode of action of WR242511 on DNA, RNA, protein and fatty acid synthesis of leishmanial cells was investigated utilizing radioactive substrates. The results suggest that it inhibits DNA synthesis initially, then RNA synthesis then declines. Protein synthesis is the last metabolic pathway to be affected. This is possibly due to the inhibition of DNA and RNA synthesis. The inhibition of fatty acid synthesis is observed after the inhibition of RNA synthesis and 2 hours after exposure to WR242511.