Discovery of a new isomannide-based peptidomimetic synthetized by Ugi multicomponent reaction as human tissue kallikrein 1 inhibitor. Issue 2 (15th January 2017)

• Record Type: Journal Article
• Authors: Barros, Thalita G.; Santos, Jorge A.N.; de Souza, Bruno E.G.; Sodero, Ana Carolina R.; de Souza, Alessandra M.T.; da Silva, Dayane P.; Rodrigues, Carlos Rangel; Pinheiro, Sergio; Dias, Luiza R.S.; Abrahim-Vieira, Bárbara; Puzer, Luciano; Muri, Estela M.F.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 2(2017)
• Page Start: 314
• Page End: 318
• Publication Date: 2017-01-15
• Subjects: Peptidomimetics -- Ugi reactions -- Kallikreins -- Inhibitors -- Molecular modeling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.11.051
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Human kallikrein 1 (KLK1) is the most extensively studied member of this family and plays a major role in inflammation processes. From Ugi multicomponent reactions, isomannide-based peptidomimetic10 and13 where synthesized and showed low micromolar values of IC50 for KLK1 The most active compound (10 ) presented competitive mechanism, with three structural modifications important to interact with active site residues which corroborates its KLK1 inhibition. Finally, the most active compound also showed good ADMET profile, which indicates compound10 as a potential hit in the search for new KLK1 inhibitors with low side effects.