Synthesis and biological evaluation of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives against the cysteine protease falcipain-2 and a chloroquine resistant strain of Plasmodium falciparum

A targeted series of phenolic Mannich bases of benzaldehyde and (thio)semicarbazone derivatives were synthesized and evaluated in vitro against the malarial cysteine protease falcipain-2 and a chloroquine resistant strain (W2) of Plasmodium falciparum. A novel series of 4-aminoquinoline semicarbazones were the most effective inhibitors of falcipain-2 (most potent inhibitor had IC50 = 0.63 μM) while a bisquinoline semicarbazone compound 8f was the most potent antimalarial compound with an IC50 of 0.07 μM against W2. Compound 8f also weakly inhibited falcipain-2, with an IC50 of 3.16 μM, although its principal antiparasitic activity did not appear to be due to inhibition of this enzyme.

A new series of phenolic Mannich bases of aminoquinoline semicarbazone and (thio)semicarbazone derivatives were synthesized and evaluated in vitro against falcipain-2 and the W2 strain of Plasmodium falciparum. All aminoquinoline semicarbazones showed antimalarial activity with IC50 in the range of 0.08–1.0 μM.Figure optionsDownload as PowerPoint slide