Abstract
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 phthalonitrile quinolines 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 µM (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.
Highlights
Osteoporosis is a systemic disease that affects bone tissue
Based on our continuing interest in potential inhibitors of cathepsins,[19,25,26,27,28,29,30] we report the synthesis and inhibitory evaluation of nine 2,4-diphenylquinolines, among them five phthalonitrilequinoline dyads as cathepsin K (CatK) inhibitors
We described the synthesis of nine 2,4-diphenylquinolines among them five phthalonitrilequinoline dyads employing a multicomponent reaction approach (MCR)
Summary
Osteoporosis is a systemic disease that affects bone tissue. This is caused by the deregulation of the bone remodeling process and causes bone loss resulting in increased bone fragility and susceptibility for fractures.[1]. The study of new therapies show that through the inhibition of the enzyme cathepsin K (CatK) it is possible to have a selective reduction of bone resorption without interfering in its formation. Based on our continuing interest in potential inhibitors (natural and/or synthetic) of cathepsins,[19,25,26,27,28,29,30] we report the synthesis and inhibitory evaluation of nine 2,4-diphenylquinolines, among them five phthalonitrilequinoline dyads (compounds which combine the structural features of quinoline and phthalonitrile nucleus) as CatK inhibitors.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
