title: Biological evaluation and docking studies of natural isocoumarins as inhibitors for human kallikrein 5 and 7.
abstract: Human kallikrein 5 and 7 (KLK5 and KLK7) are trypsin-like and chymotrypsin-like serine proteases, respectively, and promising targets for the treatment of skin desquamation, inflammation and cancer. In an effort to develop new inhibitors for these enzymes, we carried out enzymatic inhibition assays and docking studies with three isocoumarin compounds. Some promising inhibitors were uncovered, with vioxanthin and 8,8'-paepalantine being the most potent competitive inhibitors of KLK5 (K(i)=22.9 μM) and KLK7 (K(i)=12.2 μM), respectively. Our docking studies showed a good correlation with the experimental results, and revealed a distinct binding mode for the inhibitors at the binding sites of KLK5 and KLK7. In addition, the docking results suggested that the formation of hydrogen bonds at the oxyanion hole is essential for a good inhibitor.
authors: Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
authors: Thiago S P
authors: TS
authors: Teixeira
authors: Renato F
authors: RF
authors: Freitas
authors: Odonírio
authors: O
authors: Abrahão
authors: Karina F
authors: KF
authors: Devienne
authors: Lucas R
authors: LR
authors: de Souza
authors: Sachico I
authors: SI
authors: Blaber
authors: Michael
authors: M
authors: Blaber
authors: Marcia Y
authors: MY
authors: Kondo
authors: Maria A
authors: MA
authors: Juliano
authors: Luiz
authors: L
authors: Juliano
authors: Luciano
authors: L
authors: Puzer
mesh_terms: D006801:Humans; D049934:Isocoumarins / Q000737:chemistry* / Q000494:pharmacology*; D007610:Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D049934:Isocoumarins; C400147:KLK5 protein, human; C082472:KLK7 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases