title: De novo design of 7-aminocoumarin derivatives as novel falcipain-3 inhibitors.
abstract: The availability of the crystal structure of falcipain-3, knowledge of the peptides carrying the 7-aminocoumarin moiety as falcipain-3 ligands/substrates, and a need for new antimalarial agents stimulated us to look at the possibility of finding some novel falcipain-3 inhibitors. In this paper, we report the effect of substitution at the 7-amino position of the coumarin nucleus on the inhibition of falcipain-3, which is a well-validated antimalarial target. The de novo drug design was assisted by QSAR studies that shed light on the binding patterns of known and the newly designed inhibitors, thus taking this discovery process to the next level.
authors.affiliation: Department of Pharmaceutical Chemistry, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai 400 098, India.
authors.forename: Anand S
authors.initials: AS
authors.lastname: Chintakrindi
authors.forename: Mushtaque S
authors.initials: MS
authors.lastname: Shaikh
authors.forename: Evans C
authors.initials: EC
authors.lastname: Coutinho
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D008288:Malaria / Q000188:drug therapy; D008958:Models, Molecular; D010963:Plasmodium falciparum / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs; D017433:Protein Structure, Secondary; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors; D003546:Cysteine Endopeptidases; C443101:falcipain 3; C080488:7-aminocoumarin