Design and synthesis of novel 2-pyridone peptidomimetic falcipain 2/3 inhibitors.
The structure-based design, chemical synthesis and in vitro activity evaluation of various falcipain inhibitors derived from 2-pyridone are reported. These compounds contain a peptidomimetic binding determinant and a Michael acceptor terminal moiety capable of deactivating the cysteine protease active site.
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Department of Chemistry, Biochemistry and Pharmacy, and CCMAR, University of Algarve, Campus de Gambelas, Faro 8005-039, Portugal.
Berry
Neil
N
Gibbons
Peter
P
Cristiano
M Lurdes S
ML
Rosenthal
Philip J
PJ
Gut
Jiri
J
Ward
Stephen A
SA
O'Neill
Paul M
PM
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008288:Malaria / Q000188:drug therapy; D008956:Models, Chemical; D008968:Molecular Conformation; D010963:Plasmodium falciparum / Q000378:metabolism; D011728:Pyridones / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000962:Antimalarials; D015853:Cysteine Proteinase Inhibitors; D011728:Pyridones; D003546:Cysteine Endopeptidases; C416224:falcipain 2; C443101:falcipain 3