title: Chlorhexidine inhibits the activity of dental cysteine cathepsins.
abstract: The co-expression of MMPs and cysteine cathepsins in the human dentin-pulp complex indicates that both classes of enzymes can contribute to the endogenous proteolytic activity of dentin. Chlorhexidine (CHX) is an efficient inhibitor of MMP activity. This study investigated whether CHX could also inhibit cysteine cathepsins present in dentin. The inhibitory profile of CHX on the activity of dentin-extracted and recombinant cysteine cathepsins (B, K, and L) was monitored in fluorogenic substrates. The rate of substrate hydrolysis was spectrofluorimetrically measured, and inhibitory constants were calculated. Molecular docking was performed to predict the binding affinity between CHX and cysteine cathepsins. The results showed that CHX inhibited the proteolytic activity of dentin-extracted cysteine cathepsins in a dose-dependent manner. The proteolytic activity of human recombinant cathepsins was also inhibited by CHX. Molecular docking analysis suggested that CHX strongly interacts with the subsites S2 to S2' of cysteine cathepsins B, K, and L in a very similar manner. Taken together, these results clearly showed that CHX is a potent inhibitor of the cysteine cathepsins-proteolytic enzymes present in the dentin-pulp complex.
authors.affiliation: Department of Restorative Dentistry, Piracicaba Dental School, State University of Campinas, Brazil.
authors.forename: P M C
authors.initials: PM
authors.lastname: Scaffa
authors.forename: C M P
authors.initials: CM
authors.lastname: Vidal
authors.forename: N
authors.initials: N
authors.lastname: Barros
authors.forename: T F
authors.initials: TF
authors.lastname: Gesteira
authors.forename: A K
authors.initials: AK
authors.lastname: Carmona
authors.forename: L
authors.initials: L
authors.lastname: Breschi
authors.forename: D H
authors.initials: DH
authors.lastname: Pashley
authors.forename: L
authors.initials: L
authors.lastname: Tjäderhane
authors.forename: I L S
authors.initials: IL
authors.lastname: Tersariol
authors.forename: F D
authors.initials: FD
authors.lastname: Nascimento
authors.forename: M R
authors.initials: MR
authors.lastname: Carrilho
mesh_terms: D000328:Adult; D002401:Cathepsin B / Q000037:antagonists & inhibitors; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D056668:Cathepsin L / Q000037:antagonists & inhibitors; D002403:Cathepsins / Q000037:antagonists & inhibitors*; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003804:Dentin / Q000201:enzymology*; D004151:Dipeptides; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005456:Fluorescent Dyes; D006801:Humans; D006868:Hydrolysis; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins; D013050:Spectrometry, Fluorescence; D055815:Young Adult
chemical_list: D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; C021159:benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide; D002403:Cathepsins; C533912:CTSB protein, human; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; C534130:CTSK protein, human; D056657:Cathepsin K; D007930:Leucine; C010882:chlorhexidine gluconate; D002710:Chlorhexidine; C024974:E 64