benzofurans and Dental-Caries

The principal etiological agent of human dental caries, Streptococcus mutans is a multi-virulent pathogen that can transform commensal oral microbial community to plaque biofilms. Major virulence factors that are associated with the cariogenicity of S. mutans include adhesion, acidogenicity and acidurity. All these pathogenic traits coordinate and alter the dental plaque ecology which provide room for interaction with other similar acidogenic and aciduric bacteria. This cariogenic flora increases the possibility of enamel demineralization which headway to caries development. The present study was aimed at evaluating the antimicrobial and antiinfective potential of a lichen secondary metabolite usnic acid (UA) against S. mutans. Minimum inhibitory concentration (MIC), Minimum bactericidal concentration (MBC) and growth kinetics were evaluated to determine the antimicrobial potential of UA against S. mutans. UA at 5 µg mL

Topics: Bacterial Proteins; Benzofurans; Dental Caries; Down-Regulation; Gene Expression Regulation, Bacterial; Glucose; Humans; Oxidative Stress; Signal Transduction; Streptococcus mutans

Dental caries is one of the most common chronic diseases and is caused by acid fermentation of bacteria adhered to the teeth. Streptococcus mutans (S. mutans) utilizes sortase A (SrtA) to anchor surface proteins to the cell wall and forms a biofilm to facilitate its adhesion to the tooth surface. Some plant natural products, especially several flavonoids, are effective inhibitors of SrtA. However, given the limited number of inhibitors and the development of drug resistance, the discovery of new inhibitors is urgent. Here, the high-throughput virtual screening approach was performed to identify new potential inhibitors of S. mutans SrtA. Two libraries were used for screening, and nine compounds that had the lowest scores were chosen for further molecular dynamics simulation, binding free energy analysis and absorption, distribution, metabolism, excretion and toxicity (ADMET) properties analysis. The results revealed that several similar compounds composed of benzofuran, thiadiazole and pyrrole, which exhibited good affinities and appropriate pharmacokinetic parameters, were potential inhibitors to impede the catalysis of SrtA. In addition, the carbonyl of these compounds can have a key role in the inhibition mechanism. These findings can provide a new strategy for microbial infection disease therapy.

Topics: Aminoacyltransferases; Bacterial Adhesion; Bacterial Proteins; Benzofurans; Biofilms; Computer Simulation; Cysteine Endopeptidases; Dental Caries; Pyrroles; Streptococcus mutans; Thiadiazoles

The antibacterial activity of usnic acid, the most widely distributed antibiotic among the numerous ones produced by many lichen species has been re-examined and particular attention has been devoted to the activity of optically active forms of usnic acid against Streptococcus mutans. The D(+) enantiomer was found to be more active than the L(+) form and was observed to exert a rather selective activity against S. mutans. Trials carried out in volunteers showed that mouth-rinse with D(+) usnic acid preparations exerted a selective and long lasting action against S. mutans, without substantially altering the equilibrium of normal oral bacterial flora. The adherence of S. mutans to smooth surfaces is not increased by the presence of subinhibiting concentrations of D(+) usnic acid. This is at variance with what has been observed with other antibiotics. These characteristics make D(+) usnic acid a suitable candidate for topical use in oral medicine.

Topics: Benzofurans; Dental Caries; Ecology; Humans; Microbial Sensitivity Tests; Mouth; Streptococcus mutans