title: The natural flavone fukugetin as a mixed-type inhibitor for human tissue kallikreins.
abstract: The human tissue kallikreins (KLK1-KLK15) comprise a family of 15 serine peptidases detected in almost every tissue of the human body and that actively participate in many physiological and pathological events. Some kallikreins are involved in diseases for which no effective therapy is available, as for example, epithelial disorders, bacterial infections and in certain cancers metastatic processes. In recent years our group have made efforts to find inhibitors for all kallikreins, based on natural products and synthetic molecules, and all the inhibitors developed by our group presented a competitive mechanism of inhibition. Here we describe fukugetin, a natural product that presents a mixed-type mechanism of inhibition against KLK1 and KLK2. This type of inhibitor is gaining importance today, especially for the development of exosite-type inhibitors, which present potential to selectively inhibit the enzyme activity only against specific substrate.
authors: Instituto Federal de Ciência, Tecnologia e Educação do Sul de Minas Gerais, Campus Inconfidentes, MG, Brazil.
authors: Jorge A N
authors: JA
authors: Santos
authors: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Márcia Y
authors: MY
authors: Kondo
authors: Department of Biology, The Johns Hopkins University, Baltimore, MD, USA.
authors: Renato F
authors: RF
authors: Freitas
authors: Departamento de química, Universidade Federal de Viçosa, Viçosa, MG, Brazil.
authors: Marcelo H
authors: MH
authors: dos Santos
authors: Departamento de química, Universidade Federal de Lavras, Lavras, MG, Brazil.
authors: Teodorico C
authors: TC
authors: Ramalho
authors: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Diego M
authors: DM
authors: Assis
authors: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Luiz
authors: L
authors: Juliano
authors: Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors: Maria A
authors: MA
authors: Juliano
authors: Centro de Ciências Naturais e Humanas, Bloco Delta, Sala 210, Universidade Federal do ABC, Rua Arcturus 3, São Bernardo do Campo, SP 09606-070, Brazil. Electronic address: luciano.puzer@ufabc.edu.br.
authors: Luciano
authors: L
authors: Puzer
mesh_terms: D044946:Biflavonoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D029760:Garcinia / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020840:Tissue Kallikreins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D044946:Biflavonoids; D001688:Biological Products; D015842:Serine Proteinase Inhibitors; C105620:morelloflavone; D020840:Tissue Kallikreins
keywords: Enzyme; Flavone; Inhibitor; Kallikrein; Molecular docking; Molecular dynamic simulation; Serine protease