5446-83-3Relevant articles and documents
Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents
Nijampatnam, Bhavitavya,Casals, Luke,Zheng, Ruowen,Wu, Hui,Velu, Sadanandan E.
supporting information, p. 3508 - 3513 (2016/07/21)
Streptococcus mutans has been implicated as the major etiological agent in the initiation and the development of dental caries due to its robust capacity to form tenacious biofilms. Ideal therapeutics for this disease will aim to selectively inhibit the biofilm formation process while preserving the natural bacterial flora of the mouth. Several studies have demonstrated the efficacies of flavonols on S. mutans biofilms and have suggested the mechanism of action through their effect on S. mutans glucosyltransferases (Gtfs). These enzymes metabolize sucrose into water insoluble and soluble glucans, which are an integral measure of the dental caries pathogenesis. Numerous studies have shown that flavonols and polyphenols can inhibit Gtf and biofilm formation at millimolar concentrations. We have screened a group of 14 hydroxychalcones, synthetic precursors of flavonols, in an S. mutans biofilm assay. Several of these compounds emerged to be biofilm inhibitors at low micro-molar concentrations. Chalcones that contained a 3-OH group on ring A exhibited selectivity for biofilm inhibition. Moreover, we synthesized 6 additional analogs of the lead compound and evaluated their potential activity and selectivity against S. mutans biofilms. The most active compound identified from these studies had an IC50value of 44?μM against biofilm and MIC50value of 468?μM against growth displaying >10-fold selectivity inhibition towards biofilm. The lead compound displayed a dose dependent inhibition of S. mutans Gtfs. The lead compound also did not affect the growth of two commensal species (Streptococcus sanguinis and Streptococcus gordonii) at least up to 200?μM, indicating that it can selectively inhibit cariogenic biofilms, while leaving commensal and/or beneficial microbes intact. Thus non-toxic compounds have the potential utility in public oral health regimes.
Chalcones as positive allosteric modulators of α7 nicotinic acetylcholine receptors: A new target for a privileged structure
Balsera, Beatriz,Mulet, José,Fernández-Carvajal, Asia,Torre-Martínez, Roberto De La,Ferrer-Montiel, Antonio,Hernández-Jiménez, José G.,Estévez-Herrera, Judith,Borges, Ricardo,Freitas, Andiara E.,López, Manuela G.,García-López, M. Teresa,González-Mu?iz, Rosario,Pérez De Vega, María Jesús,Valor, Luis M.,Svobodová, Lucie,Sala, Salvador,Sala, Francisco,Criado, Manuel
, p. 724 - 739 (2015/02/19)
The α7 acetylcholine nicotine receptor is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain and inflammation among other diseases. Therefore, the development of new agents that target this receptor has great significance. Positive allosteric modulators might be advantageous, since they facilitate receptor responses without directly interacting with the agonist binding site. Here we report the search for and further design of new positive allosteric modulators having the relatively simple chalcone structure. From the natural product isoliquiritigenin as starting point, chalcones substituted with hydroxyl groups at defined locations were identified as optimal and specific promoters of α77 nicotinic function. The most potent compound (2,4,2-2,5-2-tetrahydroxychalcone, 111) was further characterized showing its potential as neuroprotective, analgesic and cognitive enhancer, opening the way for future developments around the chalcone structure.
