Synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives.

A new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against Leishmania donovani and Trypanosoma brucei brucei. Results from these structure-activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against L. donovani promastigotes and amastigotes parasites (IC(50) values in a range of 2-11 μM).

Selection and phenotype characterisation of sitamaquine-resistant promastigotes of Leishmania donovani.

A Leishmania donovani promastigote line resistant to 160microM sitamaquine, named SITA-160R, was selected in vitro by continuous stepwise drug pressure. SITA-160R line was able to infect murine peritoneal macrophages in vitro in the same manner as the wild-type line (WT) but was less infective for Balb/c mice than its parent WT clone. This line was about five and three times more resistant to sitamaquine than the WT line on promastigote and intramacrophage amastigote forms, respectively.