title: A chalcone with potent inhibiting activity against biofilm formation by nontypeable Haemophilus influenzae.
abstract: Nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, frequently causes biofilm infections. Currently, resistance of bacteria within the biofilm to conventional antimicrobials poses a major obstacle to effective medical treatment on a global scale. Novel agents that are effective against NTHi biofilm are therefore urgently required. In this study, a series of natural and synthetic chalcones with various chemical substituents were evaluated in vitro for their antibiofilm activities against strong biofilm-forming strains of NTHi. Of the test chalcones, 3-hydroxychalcone (chalcone 8) exhibited the most potent inhibitory activity, its mean minimum biofilm inhibitory concentration (MBIC50 ) being 16 μg/mL (71.35 μM), or approximately sixfold more active than the reference drug, azithromycin (MBIC50 419.68 μM). The inhibitory activity of chalcone 8, which is a chemically modified chalcone, appeared to be superior to those of the natural chalcones tested. Significantly, chalcone 8 inhibited biofilm formation by all studied NTHi strains, indicating that the antibiofilm activities of this compound occur across multiple strong-biofilm forming NTHi isolates of different clinical origins. According to antimicrobial and growth curve assays, chalcone 8 at concentrations that decreased biofilm formation did not affect growth of NTHi, suggesting the biofilm inhibitory effect of chalcone 8 is non-antimicrobial. In terms of structure-activity relationship, the possible substituent on the chalcone backbone required for antibiofilm activity is discussed. These findings indicate that 3-hydroxychalcone (chalcone 8) has powerful antibiofilm activity and suggest the potential application of chalcone 8 as a new therapeutic agent for control of NTHi biofilm-associated infections.
authors.affiliation: Department of Microbiology and Parasitology; Centre of Excellence in Medical Biotechnology, Faculty of Medical Science, Naresuan University, Phitsanulok, 65000.
authors.forename: Duangkamol
authors.initials: D
authors.lastname: Kunthalert
authors.forename: Sudarat
authors.initials: S
authors.lastname: Baothong
authors.forename: Pichit
authors.initials: P
authors.lastname: Khetkam
authors.forename: Suwadee
authors.initials: S
authors.lastname: Chokchaisiri
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002599:Chalcone / Q000737:chemistry / Q000494:pharmacology*; D006192:Haemophilus Infections / Q000382:microbiology; D006193:Haemophilus influenzae / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents; D002599:Chalcone
keywords: biofilm formation; chalcone; nontypeable Haemophilus influenzae; strong-biofilm producing strain