1003377-77-2

Upstream product

• 5273-86-9 C₁₂H₁₆O₃ 
• 4460-86-0 asaraldehyde 
• 100-06-1 1-(4-methoxyphenyl)ethanone 

Relevant academic research and scientific papers

Hydroxychalcone inhibitors of Streptococcus mutans glucosyl transferases and biofilms as potential anticaries agents

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.

Hansch’s analysis application to chalcone synthesis by Claisen–Schmidt reaction based in DFT methodology

Chalcones are bioactive compounds obtained from either natural sources or synthetic procedures and widely used due to their several biological properties. The most common experimental methodology in obtaining these compounds is Claisen–Schmidt reaction, which is a particular type of aldolic condensation. In this work, we have synthesized 23 chalcones and by density functional theory (DFT) calculation, we have studied the difference in reactivity of the several benzaldehydes and their effects on the yield of this reaction. From molecular orbital descriptors were obtained two quantitative structure–reactivity relationship (QSRR) models based on Hansch’s analysis. The results of this study showed that, for the most benzaldehydes (15 of 23 compounds), their reactivity was correlated with LUMO energy and global Electrophilicity Index (ω) values, which are determined in the first step of Claisen–Schmidt condensation mechanism (nucleophilic addition). Likewise, for the smallest group of benzaldehydes, their reactivity was related to their HOMO and ΔL???H (LUMO???HOMO) energies, which were determined in the second step of the mechanism (trans-elimination). This is the first report of a QSRR model analyzing the yield of chalcone synthesis based on DFT methodology.

Synthesis, characterization and antimicrobial activities of chalcones and their post transformation to pyrazole derivatives

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

ANTI-INVASIVE COMPOUNDS

The present invention relates to the field of anti-invasive compounds and methods for predicting the anti-invasive activity of said compounds, as well as their use in the prevention and/or treatment of diseases associated with undesired cell invasion; in particular, this invention relates to the field of anti-invasive chalcone-like compounds.

4-Fluoro-3′,4′,5′-trimethoxychalcone as a new anti-invasive agent. From discovery to initial validation in an in vivo metastasis model

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.

Synthesis and cytotoxic evaluation of alkoxylated chalcones

A series of chalcones a1-20 bearing a 4-OMe groups on the A-ring were initially synthesized and their anticancer activities towards HepG2 cells evaluated. Subsequently, a series of chalcones b1-42 bearing methoxy groups at the 2′ and 6′-positions of the B-ring were synthesized and their anticancer activities towards five human cancer cell lines (HepG2, HeLa, MCF-7, A549 and SW1990) and two non-tumoral human cell lines evaluated. The results showed that six compounds (b6, b8, b11, b16, b18, b22, b23 and b29) displayed promising activities, with compounds b22 and b29 in particular showing higher levels of activity than etoposide against all five cancer cell lines. Compound b29 showed a promising SI value compared with both HMLE and L02 (2.1-6.5 fold in HMLE and > 33 > 103.1 fold in L02, respectively).

Synthesis, anticancer and antioxidant activities of 2,4,5-trimethoxy chalcones and analogues from asaronaldehyde: Structure-activity relationship

2,4,5-Trimethoxy chalcones and analogues were synthesized from asaronaldehyde derived from β-asarone. These novel compounds when tested against three human tumour cell lines (MCF-7, SW-982 and HeLa) using MTT assay, revealed that chalcones possessing electron donor groups in para position to carbonyl moiety of phenyl ring A, showed better inhibitory activity (2, 3, 4, 6, 7, 10, 17). When evaluated for antioxidant activities, compound 15 exhibited better free radical scavenging property in DPPH assay while compounds 2, 3, 5, 7, 9, 10, 11, 16, and 18 showed significant NO scavenging activity. All compounds exhibited very good phenyl hydrazine induced haemolysis of erythrocytes in phenylhydrazine assay. Structure-activity relationship (SAR) study using in-silico analysis matched well with in-vitro tumour cell inhibitory activity.

Stilbene-chalcone hybrids: Design, synthesis, and evaluation as a new class of antimalarial scaffolds that trigger cell death through stage specific apoptosis

Novel stilbene-chalcone (S-C) hybrids were synthesized via a sequential Claisen-Schmidt-Knoevenagel-Heck approach and evaluated for antiplasmodial activity in in vitro red cell culture using SYBR Green I assay. The most potent hybrid (11) showed IC50