| Full text | |
| Author(s): Show less - |
Teixeira, Thiago S. P.
[1]
;
Freitas, Renato F.
[1]
;
Abrahao, Jr., Odonirio
[1]
;
Devienne, Karina F.
[1]
;
de Souza, Lucas R.
[1]
;
Blaber, Sachico I.
[2]
;
Blaber, Michael
[2]
;
Kondo, Marcia Y.
[3]
;
Juliano, Maria A.
[3]
;
Juliano, Luiz
[3]
;
Puzer, Luciano
[4, 1]
Total Authors: 11
|
| Affiliation: | [1] Univ Fed Triangulo Mineiro, Inst Ciencias Biol & Nat, Uberaba, MG - Brazil
[2] Florida State Univ, Dept Biomed Sci, Tallahassee, FL 32306 - USA
[3] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo - Brazil
[4] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Santo Andre, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Bioorganic & Medicinal Chemistry Letters; v. 21, n. 20, p. 6112-6115, OCT 15 2011. |
| Web of Science Citations: | 35 |
| 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 mu M) and KLK7 (K(i) = 12.2 mu M), 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. (C) 2011 Elsevier Ltd. All rights reserved. (AU) | |