57601-14-6

Upstream product

• 104236-80-8 (E)-1-(2,4-dihydroxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one 
• 74-88-4 methyl iodide 
• 552-41-0 1-(2-hydroxy-4-methoxyphenyl)ethanone 
• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 74645-71-9 3′,4′,7-trimethoxyflavanone 
• 107-00-6 but-1-yne 
• 77-78-1 dimethyl sulfate 
• 503-17-3 dimethylacetylene 
• 35090-88-1 (+)-3',4',7-tri-O-methylfustin 
• 89-84-9 2',4'-dihydroxy-4-acetophenone 
• 4382-36-9 (+)-Fustin 
• 5460-32-2 1-iodo-3,4-dimethoxybenzene 
• 67756-04-1 1-(2,4-dimethoxy-phenyl)-prop-2-en-1-one 
• 100753-43-3 (E)-1-(2,4-dimethoxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one 

Downstream Products

• 109469-82-1 2',5'-dihydroxy-3,4,4'-trimethoxy-trans-chalcone 
• 58544-90-4 2-(3,4-dimethoxyphenyl)-3-hydroxy-7-methoxy-4H-chromen-4-one 
• 10493-10-4 3.4.4'-trimethoxy-2'-acetoxy-trans-chalcone 
• 22395-24-0 3',4',7-trimethoxyflavone 
• 139006-37-4 cis-3-hydroxy-3',4',7-trimethoxyflavanone dimethylacetal 
• 10493-09-1 7,3',4'-trimethoxyflavanone 
• 95931-30-9 2,5-Dihydro-8-methoxy-3-(3',4'-dimethoxyphenyl)-1-benzoxepin 
• 114439-84-8 (E)-3-(3,4-Dimethoxy-phenyl)-1-(2-{2-[(E)-3-(3,4-dimethoxy-phenyl)-acryloyl]-5-methoxy-phenoxymethoxy}-4-methoxy-phenyl)-propenone 
• 76672-90-7 3-(3,4-dimethoxyphenyl)-1-(2-hydroxy-4-methoxyphenyl)-1-propanone 
• 487-52-5 3,4,2',4'-tetrahydroxy-chalcone 
• 6515-24-8 (2S,3R)-2-(3,4-Dimethoxy-phenyl)-3-hydroxy-7-methoxy-chroman-4-one 
• 85288-45-5 2'-hydroxy-3,4,4',5'-tetramethoxy-trans-chalcone 
• 50402-44-3 (2RS:3SR)-2.3-dibromo-3-(3.4-dimethoxy-phenyl)-1-(4-methoxy-2-acetoxy-phenyl)-propanone-⁽¹⁾ 
• 17093-86-6 3,3',4',7-tetra-O-methylfisetin 

Relevant academic research and scientific papers

Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors

The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC50 of 72 ± 2 nM and its 8-C-glucoside orientin with an IC50 of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 ? resolution and quambalarine B at 2.5 ? resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.

Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents

Twenty-one chalcones were prepared via aldol condensation and subsequent reduction of these compound led to the corresponding dihydrochalcone and 1,3-diphenylpropane derivatives. The synthetic products were examined for their effects on NO inhibition in L

Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds

Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2’-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, com

Optimization of Acryloylphenylcarboxamides as Inhibitors of ABCG2 and Comparison with Acryloylphenylcarboxylates

ABCG2 belongs to the superfamily of ATP binding cassette (ABC) proteins and is associated with the limited success of anticancer chemotherapy, given its responsibility for the cross-resistance of tumor cells, known as multidrug resistance (MDR). Several classes of ABCG2 inhibitors were developed for increasing the efficacy of chemotherapy. A series of chalcones coupled to an additional aromatic residue was synthesized and investigated for their inhibition of ABC transporters. In our previous work we determined the preferred position of the linker on the A-ring to be ortho, and found several substitution patterns at the additional ring that improved potency. In this study we investigated whether a methoxy group that improved the inhibitory activity of chalcones would also be beneficial for the acryloylphenylcarboxamide scaffold. Indeed, this modification led to highly potent ABCG2 inhibitors. To support the hypothesis of a beneficial effect of the amide linker, six acryloylphenylcarboxylates were synthesized and investigated for their inhibitory activity. Replacement of the amide linker with an ester group resulted in decreased inhibition. Molecular modeling showed that the conformational preference of both series differs, thereby explaining the positive effect of the amide linker. Several compounds were characterized in detail by investigating their intrinsic cytotoxicity and capacity to reverse MDR in MTT assays and their effect on vanadate-sensitive ATPase activity.

Profiling of flavonol derivatives for the development of antitrypanosomatidic drugs

Flavonoids represent a potential source of new antitrypanosomatidic leads. Starting from a library of natural products, we combined target-based screening on pteridine reductase 1 with phenotypic screening on Trypanosoma brucei for hit identification. Flavonols were identified as hits, and a library of 16 derivatives was synthesized. Twelve compounds showed EC50 values against T. brucei below 10 μM. Four X-ray crystal structures and docking studies explained the observed structure-activity relationships. Compound 2 (3,6-dihydroxy-2-(3-hydroxyphenyl)-4H-chromen-4-one) was selected for pharmacokinetic studies. Encapsulation of compound 2 in PLGA nanoparticles or cyclodextrins resulted in lower in vitro toxicity when compared to the free compound. Combination studies with methotrexate revealed that compound 13 (3-hydroxy-6-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one) has the highest synergistic effect at concentration of 1.3 μM, 11.7-fold dose reduction index and no toxicity toward host cells. Our results provide the basis for further chemical modifications aimed at identifying novel antitrypanosomatidic agents showing higher potency toward PTR1 and increased metabolic stability.

Molecular characterization, biological activity, and in silico study of 2-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-6-methoxy-4H-chromen-4-one as a novel selective COX-2 inhibitor

The present study aimed to characterize and investigate 2-(3,4-dimethoxyphenyl)-3-(4-fluorophenyl)-6-methoxy-4H-chromen-4-one (22) as a novel selective COX-2 inhibitor. The data collected from the single X-ray crystallographic analysis and in silico study

Inhibition of prostaglandin E2 production by synthetic minor prenylated chalcones and flavonoids: Synthesis, biological activity, crystal structure, and in silico evaluation

The discovery of potent inhibitors of prostaglandin E2 (PGE 2) synthesis in recent years has been proven to be an important game changer in pharmaceutical industry. It is known that excessive production of PGE2 triggers a

Synthesis and biological evaluation of flavones and benzoflavones as inhibitors of BCRP/ABCG2

Multidrug resistance (MDR) often leads to a failure of cancer chemotherapy. Breast Cancer Resistance Protein (BCRP/ABCG2), a member of the superfamily of ATP binding cassette proteins has been found to confer MDR in cancer cells by transporting molecules with amphiphilic character out of the cells using energy from ATP hydrolysis. Inhibiting BCRP can be a solution to overcome MDR.We synthesized a series of flavones, 7,8-benzofl avones and 5,6-benzo flavones with varying substituents at positions 3, 3′ and 4′ of the (benzo)fl avone structure. All synthesized compounds were tested for BCRP inhibition in Hoechst 33342 and pheophorbide A accumulation assays using MDCK cells expressing BCRP. All the compounds were further screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity by calcein AM accumulation assay to check the selectivity towards BCRP. In addition most active compounds were investigated for their cytotoxicity. It was observed that in most cases 7,8-benzoflavones are more potent in comparison to the 5,6-benzoflavones. In general it was found that presence of a 3-OCH3 substituent leads to increase in activity in comparison to presence of OH or no substitution at position 3. Also, it was found that presence of 3′,4′-OCH3 on phenyl ring lead to increase in activity as compared to other substituents. Compound 24, a 7,8-benzoflavone derivative was found to be most potent being 50 times selective for BCRP and showing very low cytotoxicity at higher concentrations.

Investigation of chalcones and benzochalcones as inhibitors of breast cancer resistance protein

Breast cancer resistance protein (BCRP/ABCG2) belongs to the ATP binding cassette family of transport proteins. BCRP has been found to confer multidrug resistance in cancer cells. A strategy to overcome resistance due to BCRP overexpression is the investigation of potent and specific BCRP inhibitors. The aim of the current study was to investigate different multi-substituted chalcones for their BCRP inhibition. We synthesized chalcones and benzochalcones with different substituents (viz. OH, OCH3, Cl) on ring A and B of the chalcone structure. All synthesized compounds were tested by Hoechst 33342 accumulation assay to determine inhibitory activity in MCF-7 MX and MDCK cells expressing BCRP. The compounds were also screened for their P-glycoprotein (P-gp) and Multidrug resistance-associated protein 1 (MRP1) inhibitory activity in the calcein AM accumulation assay and were found to be selective towards inhibition of BCRP. Substituents at position 2′ and 4′ on chalcone ring A were found to be essential for activity; additionally there was a great influence of substituents on ring B. Presence of 3,4-dimethoxy substitution on ring B was found to be optimal, while presence of 2- and 4-chloro substitution also showed a positive effect on BCRP inhibition.

Synthesis and anti Methicillin resistant Staphylococcus aureus activity of substituted chalcones alone and in combination with non-beta-lactam antibiotics

A total of 30 chalcone analogues was synthesized via a base catalyzed Claisen Schmidt condensation and screened for their in vitro antibacterial activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus (MRSA) alone or in combination with non beta-lactam antibiotics namely ciprofloxacin, chloramphenicol, erythromycin, vancomycin, doxycycline and gentamicin. In the checkerboard technique, fractional inhibitory concentration indices (FICI) show that the following combinations like ciprofloxacin with 25 (4′-bromo-2-hydroxychalcone); doxycycline with 21 (4-hydroxychalcone); doxycycline with 25; and doxycycline with 4 (2′,2-dihydroxychalcone) were synergistic against MRSA. In term SAR study, the relationship between chalcone structure and their antibacterial activity against S. aureus and synergy with tested antibiotics were discussed. Possible mechanisms for antibacterial activity of chalcones alone as well as the synergistic effect in combinations were proposed by molecular modeling studies, respectively. Combinations of chalcones with conventional antibiotics could be an effective alternative in the treatment of infection caused by MRSA.