title: Synthesis and evaluation of isatins and thiosemicarbazone derivatives against cruzain, falcipain-2 and rhodesain.
abstract: While commercial isatins were practically inactive against the target proteases, thiosemicarbazone derivatives were found to be active. The most active compound from the series displayed an inhibitory IC(50) value of 1 microM against rhodesain. One thiosemicarbazone was found to be active against all three proteases with inhibitory IC(50) values of 10 microM or less. A combination of N-benzylation and appropriate substitution on the aromatic portion of the isatin scaffold was generally found to be beneficial especially against cruzain for ketone inhibitors.
mesh_terms: D004353:Drug Evaluation, Preclinical; D007510:Isatin / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D011480:Protease Inhibitors; D013882:Thiosemicarbazones; D007510:Isatin