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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

New Synthetic Quinolines as Cathepsin K Inhibitors

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Silva, Taynara L. [1, 2, 3] ; Bartolomeu, Aloisio de A. [1] ; de Jesus, Hugo C. R. [1] ; de Oliveira, Kleber T. [1] ; Fernandes, Joao B. [1] ; Bromme, Dieter [2, 3] ; Vieira, Paulo C. [4, 1]
Total Authors: 7
[1] Univ Fed Sao Carlos, Dept Quim, Km 235, 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 Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Journal of the Brazilian Chemical Society; v. 31, n. 8, p. 1605-1613, AUG 2020.
Web of Science Citations: 0

Cathepsin K is a papain-like cysteine protease and is responsible for collagen degradation in bone tissue and thus represents an important target for the development of new therapies for treating diseases such as osteoporosis. Quinolines are an important class of heterocyclic molecular leads with a great pharmacological potential and represent a relevant scaffold to explore the chemical space of cathepsin K (CatK) inhibitors. This study presents the synthesis of nine 2,4-diphenylquinolines. including five ph thalonitrile quinolincs dyads, and the evaluation of their CatK inhibitory activity. Among the evaluated compounds, 4b was the most potent inhibitor with an IC50 (half-maximal inhibitory concentration) value of 1.55 mu M (against Z-Phe-Arg-MCA substrate) acting in an uncompetitive inhibition mode. Molecular docking studies provided important information on the interaction of the inhibitor with the enzyme showing that these quinoline derivatives can play an important role as CatK inhibitors. (AU)

FAPESP's process: 12/11819-8 - Chemical study of Bowdichia virgilioides (Fabaceae) on searching for selective inhibitors of cysteine peptidases.
Grantee:Taynara Lopes Silva
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/00106-7 - Photocatalyzed Reactions by using porphyrins and continuous flow conditions: Arylations of heterocycles and activated olefins.
Grantee:Kleber Thiago de Oliveira
Support type: Regular Research Grants
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 type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 14/24506-3 - Synthesis of high conjugated phthalocyanine and porphyrin derivatives: strategies using RMCs and Diels-Alder reactions
Grantee:Aloisio de Andrade Bartolomeu
Support type: Scholarships in Brazil - Doctorate