1849-58-7

Upstream product

• 118-93-4 o-hydroxyacetophenone 
• 587-04-2 m-Chlorobenzaldehyde 

Downstream Products

• 1849-59-8 2-(3'-chlorophenyl)-2,3-dihydro-4H-chromen-4-one 
• 1657006-96-6 C₁₈H₁₅ClO₂ 
• 1657006-76-2 C₁₈H₁₅Br₂ClO₂ 
• 112980-35-5 (Z)-2-(3-chlorobenzylidene)benzofuran-3(2H)-one 
• 105279-17-2 (2Z) 2-(1-(3-chlorophenyl)methylene)benzofuran-3(2H)-one 
• 1849-59-8 (+)-2-(3-chlorophenyl)chroman-4-one 

Relevant academic research and scientific papers

SAR studies of o-hydroxychalcones and their cyclized analogs and study them as novel inhibitors of cathepsin B and cathepsin H

Cathepsins have emerged as a potential target for anti-cancer drug development. In the present study, we have synthesized three structurally related series of flavanoids i.e., 2′-hydroxychalcones, flavanones and flavones and assayed in vitro to study their inhibitory potency against cathepsin B and H, promising drug candidate for cancer therapy. Enzyme kinetics studies were carried out in presence of these compounds after preliminary proteolytic studies on endogenous protein substrates. SAR studies suggested that open chain flavanoids were better inhibitors as compared to their cyclized analogs. The most potent inhibitors among the three series were nitro substituted compounds 1g, 2g and 3g with Ki values of ～6.18 × 10-8 M, 4.8 × 10-7 M and 7.85 × 10-7 M for cathepsin B and Ki values of ～2.8 × 10-7 M, 31.8 × 10-6 M and 33.7 × 10 -6 M for cathepsin H, respectively. The relationship between chalcone, flavanones and flavone structures interpreted by docking studies on cathepsin B and H also provided useful insights.

Stereoselective reduction of flavanones by marine-derived fungi

Biotransformation is an alternative with great potential to modify the structures of natural and synthetic flavonoids. Therefore, the bioreduction of synthetic halogenated flavanones employing marine-derived fungi was described, aiming the synthesis of flavan-4-ols 3a-g with high enantiomeric excesses (ee) of both cis- and trans-diastereoisomers (up to >99% ee). Ten strains were screened for reduction of flavanone 2a in liquid medium and in phosphate buffer solution. The most selective strains Cladosporium sp. CBMAI 1237 and Acremonium sp. CBMAI1676 were employed for reduction of flavanones 2a-g. The fungus Cladosporium sp. CBMAI 1237 presented yields of 72–87% with 0–64% ee cis and 0–30% ee trans with diastereoisomeric ratio (dr) from 52:48 to 64:36 (cis:trans). Whereas Acremonium sp. CBMAI 1676 resulted in 31% yield with 77–99% ee of the cis and 95–99% ee of the trans-diastereoisomers 3a-g with a dr from 54:46 to 96:4 (cis:trans). To our knowledge, this is the first report of the brominated flavon-4-ols 3e and 3f. The use of fungi, with emphasis for these marine-derived strains, is an interesting approach for enantioselective reduction of halogenated flavanones. Therefore, this strategy can be explored to obtain enantioenriched compounds with biological activities.

In quest of small-molecules as potent non-competitive inhibitors against influenza

A series of scaffolds namely aurones, 3-indolinones, 4-quinolones and cinnamic acid-piperazine hybrids, was designed, synthesized and investigated in vitro against influenza A/H1N1pdm09 virus. Designed molecules adopted different binding mode i.e., in 430-cavity of neuraminidase, unlike sialic acid and oseltamivir in molecular docking studies. All molecules reduced the viral titer and exhibited non-cytotoxicity along with cryo-protective property towards MDCK cells. Molecules (Z)-2-(3′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2f), (Z)-2-(4′-Chloro-benzylidene)-1,2-dihydro-indol-3-one (2g) and 2-(2′-Methoxy-phenyl)-1H-quinolin-4-one (3a) were the most interesting molecules identified in this research, endowed with robust potencies showing low-nanomolar EC50 values of 4.0 nM, 6.7 nM and 4.9 nM, respectively, compared to reference competitive and non-competitive inhibitors: oseltamivir (EC50 = 12.7 nM) and quercetin (EC50 = 0.56 μM), respectively. Besides, 2f, 2g and 3a exhibited good neuraminidase inhibitory activity in sub-micromolar range (IC50 = 0.52 μM, 3.5 μM, 1.3 μM respectively). Moreover, these molecules were determined as non-competitive inhibitors similar to reference non-competitive inhibitor quercetin unlike reference competitive inhibitor oseltamivir in kinetics studies.

Mycobactin Analogues with Excellent Pharmacokinetic Profile Demonstrate Potent Antitubercular Specific Activity and Exceptional Efflux Pump Inhibition

In this study, we have designed and synthesized pyrazoline analogues that partially mimic the structure of mycobactin, to address the requirement of novel therapeutics to tackle the emerging global challenge of antimicrobial resistance (AMR). Our investigation resulted in the identification of novel lead compounds 44 and 49 as potential mycobactin biosynthesis inhibitors against mycobacteria. Moreover, candidates efficiently eradicated intracellularly surviving mycobacteria. Thermofluorimetric analysis and molecular dynamics simulations suggested that compounds 44 and 49 bind to salicyl-AMP ligase (MbtA), a key enzyme in the mycobactin biosynthetic pathway. To the best of our knowledge, these are the first rationally designed mycobactin inhibitors to demonstrate an excellent in vivo pharmacokinetic profile. In addition, these compounds also exhibited more potent whole-cell efflux pump inhibition than known efflux pump inhibitors verapamil and chlorpromazine. Results from this study pave the way for the development of 3-(2-hydroxyphenyl)-5-(aryl)-pyrazolines as a new weapon against superbug-associated AMR challenges.

Design, synthesis and biological evaluation of substituted flavones and aurones as potential anti-influenza agents

We designed a series of substituted flavones and aurones as non-competitive H1N1 neuraminidase (NA) inhibitors and anti-influenza agents. The molecular docking studies showed that the designed flavones and aurones occupied 150-cavity and 430-cavity of H1N1-NA. We then synthesized these compounds and evaluated these for cytotoxicity, reduction in H1N1 virus yield, H1N1-NA inhibition and kinetics of inhibition. The virus yield reduction assay and H1N1-NA inhibition assay demonstrated that the compound 1f (4-methoxyflavone) had the lowest EC50 of 9.36 nM and IC50 of 8.74 μM respectively. Moreover, kinetic studies illustrated that compounds 1f and 2f had non-competitive inhibition mechanism.

Structure-aided drug development of potential neuraminidase inhibitors against pandemic H1N1 exploring alternate binding mechanism

Abstract: The rate of mutability of pathogenic H1N1 influenza virus is a threat. The emergence of drug resistance to the current competitive inhibitors of neuraminidase, such as oseltamivir and zanamivir, attributes to a need for an alternative approach. The design and synthesis of new analogues with alternate approach are particularly important to identify the potential neuraminidase inhibitors which may not only have better anti-influenza activity but also can withstand challenge of resistance. Five series of scaffolds, namely aurones (1a–1e), pyrimidine analogues (2a–2b), cinnamic acid analogues (3a–3k), chalcones (4a–4h) and cinnamic acid linkages (5a–5c), were designed based on virtual screening against pandemic H1N1 virus. Molecular modelling studies revealed that the designed analogues occupied 430-loop cavity of neuraminidase. Docking of sialic acid in the active site preoccupied with the docked analogues, i.e. in 430-loop cavity, resulted in displacement of sialic acid from its native pose in the catalytic cavity. The favourable analogues were synthesized and evaluated for the cytotoxicity and cytopathic effect inhibition by pandemic H1N1 virus. All the designed analogues resulting in displacement of sialic acid suggested alternate binding mechanism. Overall results indicated that aurones can be measured best among all as potential neuraminidase inhibitor against pandemic H1N1 virus. Graphical abstract: [Figure not available: see fulltext.].

Ruthenium(II)-Catalyzed Synthesis of Spirobenzofuranones by a Decarbonylative Annulation Reaction

The first decarbonylative insertion of an alkyne through C?H/C?C activation of six-membered compounds is reported. The Ru-catalyzed reaction of 3-hydroxy-2-phenyl-chromones with alkynes works most efficiently in the presence of the ligand PPh3 to provide spiro-indenebenzofuranones. Unlike previously reported metal-catalyzed decarbonylative annulation reactions, in the present decarbonylative annulation reaction, the annulation occurs before extrusion of carbon monoxide.

Design, synthesis, biological evaluation, structure-activity relationship study, and mode of action of 2-phenol-4,6-dichlorophenyl-pyridines

Human DNA topoisomerases (Topos) are essential nuclear enzyme whose level of expression is potential indicator for prediction of responsive result of chemotherapy. Topos has become a key cellular target for most of the anticancer agents that regulates top

Synthesis, crystal structure and antitumour activity evaluation of 1H-thieno[2,3-c]chromen-4(2H)-one derivatives

A series of 1H-thieno[2,3-c]chromen-4(2H)-one derivatives were synthesised through Knoevenagel condensation of substituted flavanones with thiazolidine-2,4-dione in ethanol in the presence of piperidine. The mechanism of the reaction was proposed. All synthesised compounds were characterised by IR, 1H NMR, 13C NMR, HRMS, and elemental analysis. The structure of 2-(3-chlorophenyl)-1H-thieno[2,3-c]chromen-4(2H)-one was confirmed by a single crystal X-ray diffraction analysis. A preliminary antitumour screening showed that 2-(2-fluorophenyl)-1H-thieno [2,3-c]chromen-4(2H)-one had moderate to good activity against A549, BGC-823, HCT116 and MDA-MB-453 cancer cell lines, and 2-(3,4-dimethoxyphenyl)-1H-thieno[2,3-c]chromen-4(2H)-one displayed similar activity against these four kinds of cancer cells compared with the reference drug.

Dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines: Topoisomerase I and IIα dual inhibitors with DNA non-intercalative catalytic activity

With the aim to develop novel antiproliferative agents, a new series of eighteen dihydroxylated 2,6-diphenyl-4-chlorophenylpyridines were systematically designed, prepared, and investigated for their topoisomerase (topo) I and IIα inhibitory properties an