Linear and cyclic dipeptides with antimalarial activity

Several natural and synthetic polypeptides possess important antimalarial activity. Shorter peptides with potent antimalarial activity have also been described, among them linear di-, tri-, tetra- and pentapeptides and their cyclic analogs. In an attempt to find dipeptides with antimalarial activities we show that linear and cyclic dipeptides, the latter known as diketopiperazines, still retain the fundamental core to preserve antimalarial activity. Thirteen linear dipeptides and ten diketopiperazines were investigated. Eight linear dipeptides showed IC50 values between 2.78 and 7.07 mu M, while eight diketopiperazines were also active with IC50 values between 2.26 and 4.26 mu M on Plasmodium berghei schizont cultures. (C) 2012 Elsevier Ltd. All rights reserved.