1003377-77-2Relevant 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.
, p. 3508 - 3513 (2016)
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.
Synthesis, characterization and antimicrobial activities of chalcones and their post transformation to pyrazole derivatives
Ramyashree,Raghavendra,Dileep Kumar,Vagish,Ajay Kumar
, p. 1538 - 1542 (2017/05/29)
An efficient procedure for the synthesis of trisubstituted pyrazoles was developed. Claisen-Schmidt condensation of 2,4,5-trimethoxybenzaldehyde and substituted acetophenone in the presence of aqueous alkaline bases produced chalcones. The cyclocondensati
4-Fluoro-3′,4′,5′-trimethoxychalcone as a new anti-invasive agent. From discovery to initial validation in an in vivo metastasis model
Roman, Bart I.,De Ryck, Tine,Patronov, Atanas,Slavov, Svetoslav H.,Vanhoecke, Barbara W.A.,Katritzky, Alan R.,Bracke, Marc E.,Stevens, Christian V.
supporting information, p. 627 - 639 (2015/08/03)
Invasion and metastasis are responsible for 90% of cancer-related mortality. Herein, we report on our quest for novel, clinically relevant inhibitors of local invasion, based on a broad screen of natural products in a phenotypic assay. Starting from micromolar chalcone hits, a predictive QSAR model for diaryl propenones was developed, and synthetic analogues with a 100-fold increase in potency were obtained. Two nanomolar hits underwent efficacy validation and eADMET profiling; one compound was shown to increase the survival time in an artificial metastasis model in nude mice. Although the molecular mechanism(s) by which these substances mediate efficacy remain(s) unrevealed, we were able to eliminate the major targets commonly associated with antineoplastic chalcones.
