Novel peptidomimetic cysteine protease inhibitors as potential antimalarial agents.
The synthesis of a new class of peptidomimetics 1a-j, based on a 1,4-benzodiazepine scaffold and on a C-terminal aspartyl aldehyde building block, is described. Compounds 1a-j provided significant inhibitory activity against falcipains 2A and 2B (FP-2A and FP-2B), two cysteine proteases from Plasmodium falciparum.
Micale
Nicola
N
Dipartimento Farmaco Chimico, University of Messina, Viale Annunziata, 98168, Messina, Italy. nmicale@pharma.unime.it
Kozikowski
Alan P
AP
Ettari
Roberta
R
Grasso
Silvana
S
Zappalà
Maria
M
Jeong
Jong-Jin
JJ
Kumar
Ajay
A
Hanspal
Manjit
M
Chishti
Athar H
AH
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry; D003546:Cysteine Endopeptidases / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D010963:Plasmodium falciparum / Q000201:enzymology; D013329:Structure-Activity Relationship
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D010455:Peptides; D001569:Benzodiazepines; D001224:Aspartic Acid; C006644:aspartic semialdehyde; D003546:Cysteine Endopeptidases; C416224:falcipain 2