Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Green asymmetric synthesis of epoxypeptidomimetics and evaluation as human cathepsin K inhibitors

Full text
Author(s):
Silva, Taynara L. [1, 2, 3] ; dos Santos, Deborah A. [4] ; de Jesus, Hugo C. R. [1] ; Bromme, Dieter [2, 3] ; Fernandes, Joao B. [1] ; Paixao, Marcio W. [4] ; Correa, Arlene G. [4] ; Vieira, Paulo C. [5, 4]
Total Authors: 8
Affiliation:
[1] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil
[2] Fac Dent, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3 - Canada
[3] UBC Ctr Blood Res, 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3 - Canada
[4] Univ Fed Sao Carlos, Ctr Excellence Res Sustainable Chem, Dept Chem, BR-13565905 Sao Carlos, SP - Brazil
[5] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Bioorganic & Medicinal Chemistry; v. 28, n. 15 AUG 1 2020.
Web of Science Citations: 0
Abstract

Cathepsin K (CatK) is a cysteine protease known for its potent collagenolytic activity, being recognized as an important target to the development of therapies for the treatment of bone disorders. Epoxypeptidomimetics have been reported as potent inhibitors of cathepsins, thus in this work we present a green synthesis of new peptidomimetics by using a one-pot asymmetric epoxidation/Ugi multicomponent reaction. The compounds were evaluated against CatK showing selectivity when compared with cathepsin L, with an inhibition profile in the low micromolar IC50 range. Investigation of the mechanism of action carried out for compounds LSPN428 and LSPN694 suggested a mixed inhibition mode and docking studies allowed a better understanding about interactions of inhibitors with the enzyme. (AU)

FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
Grantee:Arlene Gonçalves Corrêa
Support Opportunities: Research Grants - Research Centers in Engineering Program
FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/15455-4 - Contribution to integrated studies for leaf-cutting ants control: search for new insecticides and fungicides - nanoencapsulation
Grantee:Hugo César Ramos de Jesus
Support Opportunities: Scholarships in Brazil - Post-Doctoral