| Full text | |
| Author(s): |
de Souza, Acacio S.
[1]
;
Pacheco, Barbara D. C.
[1]
;
Pinheiro, Sergio
[1]
;
Muri, Estela M. F.
[2]
;
Dias, Luiza R. S.
[2]
;
Lima, Camilo H. S.
[2]
;
Garrett, Rafael
[3]
;
de Moraes, Mariana B. M.
[3]
;
de Souza, Bruno E. G.
[4]
;
Puzer, Luciano
[4]
Total Authors: 10
|
| Affiliation: | [1] Univ Fed Fluminense, Inst Quim, Outeiro S Joao Batista S-N, BR-24020141 Niteroi, RJ - Brazil
[2] Univ Fed Fluminense, Fac Farm, Dept Tecnol Farmaceut, Niteroi, RJ - Brazil
[3] Univ Fed Rio de Janeiro, Inst Quim, Rio De Janeiro, RJ - Brazil
[4] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Bioorganic & Medicinal Chemistry Letters; v. 29, n. 9, p. 1094-1098, MAY 1 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Human kallikreins 5 and 7 (KLK5 and KLK7) exhibit trypsin-and chymotrypsin-like activities and are involved in pathologies related to skin desquamation process. A series of new 3-acyltetramic acids were developed as a novel class of inhibitors of KLK5, KLK7 and trypsin enzymes. The nature and length of the acyl chain is crucial to the KLK5, KLK7 and trypsin inhibition activities, and the most potent compounds (but not the most selective) 2b, 2c and 2g showed low micromolar IC50 values. While very few of the compounds were selective for KLK5, the selective inhibition of trypsin against chymotrypsin was achieved. Our molecular modelling studies revealed that the double bond in 2g provided the best fit in the binding site of KLK5, while the hydrogen bonding interactions modulated the best fit of 2c in the binding site of KLK7 due to the hydrophobicity of the cavity. (AU) | |
| FAPESP's process: | 16/21441-3 - Development of Inhibitors for Human Tissue Kallikreins |
| Grantee: | Luciano Puzer |
| Support Opportunities: | Regular Research Grants |