118267-80-4

Upstream product

• 90-24-4 2-hydroxy-4,6-dimethoxyacetophenone 
• 135-02-4 ortho-anisaldehyde 
• 579-74-8 2-Methoxyacetophenone 

Downstream Products

• 109469-74-1 5,7-dimethoxy-2-(2-methoxy-phenyl)-chroman-4-one 
• 109309-38-8 4,6-dimethoxy-2-(2'-methoxybenzylidene)benzofuran-3(2H)-one 
• 109248-43-3 5-hydroxy-7-methoxy-2-(2-methoxy-phenyl)-chroman-4-one 

Relevant academic research and scientific papers

Flavokawains B and C, melanogenesis inhibitors, isolated from the root of Piper methysticum and synthesis of analogs

The ethanolic extract of the root of Piper methysticum was found to inhibit melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were isolated from this extract based on their anti-melanogenesis activity and found to inhibit melanogenesis with IC50 values of 7.7 μM and 6.9 μM, respectively. Flavokawain analogs were synthesized through a Claisen-Schmidt condensation of their corresponding acetophenones and benzaldehydes and were evaluated in terms of their tyrosinase inhibitory and anti-melanogenesis activities. Compound 1b was the most potent of these with an IC50 value of 2.3 μM in melanogenesis inhibition assays using MSH-activated B16 melanoma cells.

Application of human PCID2 protein in preparation or screening of anti-tumor drugs and compound with anti-tumor activity

The invention belongs to the technical field of biotechnology and gene therapy, and particularly relates to application of human PCID2 protein in preparation or screening of anti-tumor drugs and an anti-tumor compound. It is found that the PCID2 gene promotes tumor cell proliferation and regulates the cell cycle, is a key molecule for regulating tumor generation and development, and can be used as a target protein for preparing or screening anti-tumor drugs; meanwhile, human PCID2 protein is used as target protein, a class of PCID2 protein targeting antitumor compounds are screened out through a molecular docking technology, and the compounds can significantly inhibit tumor cell proliferation and promote tumor cell apoptosis.

Design, synthesis and docking studies of flavokawain B type chalcones and their cytotoxic effects on MCF-7 and MDA-MB-231 cell lines

Flavokawain B (1) is a natural chalcone extracted from the roots of Piper methysticum, and has been proven to be a potential cytotoxic compound. Using the partial structure of flavokawain B (FKB), about 23 analogs have been synthesized. Among them, compounds 8, 13 and 23 were found in new FKB derivatives. All compounds were evaluated for their cytotoxic properties against two breast cancer cell lines, MCF-7 and MDA-MB-231, thus establishing the structure-activity relationship. The FKB derivatives 16 (IC50 = 6.50 ± 0.40 and 4.12 ± 0.20 μg/mL), 15 (IC50 = 5.50 ± 0.35 and 6.50 ± 1.40 μg/mL) and 13 (IC50 = 7.12 ± 0.80 and 4.04 ± 0.30 μg/mL) exhibited potential cytotoxic effects on the MCF-7 and MDA-MB-231 cell lines. However, the methoxy group substituted in position three and four in compound 2 (IC50 = 8.90 ± 0.60 and 6.80 ± 0.35 μg/mL) and 22 (IC50 = 8.80 ± 0.35 and 14.16 ± 1.10 μg/mL) exhibited good cytotoxicity. The lead compound FKB (1) showed potential cytotoxicity (IC50 = 7.70 ± 0.30 and 5.90 ± 0.30 μg/mL) against two proposed breast cancer cell lines. It is evident that the FKB skeleton is unique for anticancer agents, additionally, the presence of halogens (Cl and F) in position 2 and 3 also improved the cytotoxicity in FKB series. These findings could help to improve the future drug discovery process to treat breast cancer. A molecular dynamics study of active compounds revealed stable interactions within the active site of Janus kinase. The structures of all compounds were determined by 1H-NMR, EI-MS, IR and UV and X-ray crystallographic spectroscopy techniques.

Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives

22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2′,3,4′,6′-tetramethoxychalcone (FKd 19). FKd induced a G1/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24?h-effect on Akt/mTor normal cells versus a 48?h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents.

Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication

Herein, we report a synthetic method with improved selectivity for 5-substituted flavonols via the Algar-Flynn-Oyamada reaction (AFO), by using of sodium carbonate/hydrogen peroxide A series of 5-substituted flavonols was obtained with moderate to high yields. The mechanism of the AFO reaction was elucidated. LCMS analysis and in situ 1H NMR analysis indicated that the epoxide was involved in the transformation from chalcone to flavonol and/or aurone under alkaline base/peroxide conditions.

Aurones as histone deacetylase inhibitors: Identification of key features

In this study, a total of 22 flavonoids were tested for their HDAC inhibitory activity using fluorimetric and BRET-based assays. Four aurones were found to be active in both assays and showed IC50 values below 20 μM in the enzymatic assay. Molecular modelling revealed that the presence of hydroxyl groups was responsible for good compound orientation within the isoenzyme catalytic site and zinc chelation.

Investigation of chalcones as selective inhibitors of the breast cancer resistance protein: Critical role of methoxylation in both inhibition potency and cytotoxicity

ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 μM and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6′-hydroxyl-2′,4′-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.

Natural and synthetic 2′-hydroxy-chalcones and aurones: Synthesis, characterization and evaluation of the antioxidant and soybean lipoxygenase inhibitory activity

A series of 2′-hydroxy-chalcones and their oxidative cyclization products, aurones, have been synthesized and tested for their antioxidant and lipoxygenase inhibitory activity. The natural product aureusidin (31) was synthesized in high yield by a new approach. An extensive structure-relationship study was performed and revealed that several chalcones and aurones possess an appealing pharmacological profile combining high antioxidant and lipid peroxidation activity with potent soybean LOX inhibition.

Antimitotic and antiproliferative activities of chalcones: Forward structure-activity relationship

A series of 59 chalcones was prepared and evaluated for the antimitotic effect against K562 leukemia cells. The most active chalcones were evaluated for their antiproliferative activity against a panel of 11 human and murine cell cancer lines. We found that three chalcones were of great interest as potential antimitotic drugs. In vivo safety studies conducted on one of the most active chalcones revealed that the compound was safe, allowing further in vivo antitumor evaluation.

Synthesis of 2-Benzylidene-3(2H)-benzofuran-3-ones (Aurones) by Oxidation of 2'-Hydroxychalcones with Mercury(II) Acetate

The reaction of 2'-hydroxychalcones with mercury(II) acetate in acetic acid gives predominantly 2-benzylidene-3(2H)-benzofuran-3-ones (aurones) in 28-62 percent yield accompanied by flavonones in 5-21 percent yield.