Author/Authors :
Sandra Gemma، نويسنده , , Gagan Kukreja، نويسنده , , Giuseppe Campiani، نويسنده , , Stefania Butini، نويسنده , , Matteo Bernetti، نويسنده , , Bhupendra P. Joshi، نويسنده , , Luisa Savini، نويسنده , , Nicoletta Basilico، نويسنده , , Donatella Taramelli، نويسنده , , Vanessa Yardley، نويسنده , , Alessia Bertamino، نويسنده , , Ettore Novellino، نويسنده , , Marco Persico، نويسنده , , Bruno Catalanotti، نويسنده , , Caterina Fattorusso، نويسنده ,
Abstract :
The design, synthesis, and antiplasmodial activity of antimalarial heterodimers based on the 1,4-bis(3-aminopropyl)piperazine linker is reported. In this series key structural elements derived from quinoline antimalarials were coupled to fragments capable of coordinating metal ions. Biological evaluation included determination of activity against chloroquine-sensitive and chloroquine-resistant Plasmodium falciparum strains. Some of the novel compounds presented high activity in vitro against chloroquine-resistant strains, more potent than chloroquine and clotrimazole. Computational studies revealed that the activity is likely due to the ability of the compounds to assume a multisite iron coordinating geometry.
