title: Evaluation of flavonols and derivatives as human cathepsin B inhibitor.
abstract: Cathepsin B (catB) is a cysteine protease involved in tumour progression and represents a potential therapeutic target in cancer. Among the 15 evaluated extracts from cerrado biome, Myrcia lingua Berg. (Myrtaceae) extract demonstrated to be a source of compounds with potential to inhibit catB. Using bioactivity-guided fractionation, we have found flavonols as inhibitors and also some other derivatives were obtained. From the evaluated compounds, myricetin (5) and quercetin (6) showed the most promising results with IC50 of 4.9 and 8.2 μM, respectively, and mode of inhibition as uncompetitive on catB. The results demonstrated polyhydroxylated flavonols as promising inhibitors of catB.
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: Suelem D
authors.initials: SD
authors.lastname: Ramalho
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: Lorena R F
authors.initials: LR
authors.lastname: de Sousa
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: Marcela C M
authors.initials: MC
authors.lastname: Burger
authors.affiliation: b Department de Botany , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: Maria Inês S
authors.initials: MI
authors.lastname: Lima
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: M Fátima das G F
authors.initials: MF
authors.lastname: da Silva
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: João B
authors.initials: JB
authors.lastname: Fernandes
authors.affiliation: a Department of Chemistry , Federal University of São Carlos , 13565-905 São Carlos , SP , Brazil.
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Vieira
mesh_terms: D002401:Cathepsin B / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000737:chemistry; D044948:Flavonols / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D031641:Myrica / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry
chemical_list: D005419:Flavonoids; D044948:Flavonols; D010936:Plant Extracts; C040015:myricetin; D011794:Quercetin; D002401:Cathepsin B
keywords: cathepsin B; flavonoids; uncompetitive inhibitor