37308-75-1

Usage

Uses

Used in Pharmaceutical Industry:
Flavokawain C is used as a potential anticancer agent for its ability to inhibit cell cycle progression and promote apoptosis in specific cancer cell lines, such as HCT 116 cells. This makes it a promising candidate for further research and development in the fight against cancer.
Used in Drug Development:
Flavokawain C is used as a lead compound in the development of dual inhibitors against Histone deacetylase enzymes (HDACs) and NF-κB. These dual inhibitors have the potential to target multiple pathways involved in cancer progression, making them an attractive option for the development of novel cancer therapies.
Used in Natural Product Research:
As a naturally occurring chalcone found in the kava plant, Flavokawain C is used in the study of natural products for their potential therapeutic applications. This research can lead to the discovery of new compounds and mechanisms that can be harnessed for the development of new drugs and treatments for various diseases, including cancer.

Upstream product

• 19158-99-7 2’,4’-dimethoxy-6’-hydroxy-4-O-benzylchalcone 
• 123-08-0 4-hydroxy-benzaldehyde 
• 4397-53-9 p-benzyloxybenzaldehyde 
• 90-24-4 2-hydroxy-4,6-dimethoxyacetophenone 
• 108-73-6 3,5-dihydroxyphenol 
• 77184-69-1 2’,4’-dimethoxy-6’-hydroxy-4-O-methoxymethylchalcone 
• 62014-87-3 helichrysetin 
• 74-88-4 methyl iodide 

Downstream Products

• 69127-80-6 3-(4-hydroxyphenyl)-5,7-dimethoxychromen-4-one 
• 26207-67-0 2-(4-hydroxyphenyl)-5,7-dimethoxychroman-4-one 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of dimethyl cardamonin (DMC) derivatives as P-glycoprotein-mediated multidrug resistance reversal agents

Background: P-glycoprotein (P-gp) has been regarded as an important factor in the multidrug resistance (MDR) of tumor cells within the last decade, which can be solved by inhibiting P-gp to reverse MDR. Thus, it is an effective strategy to develop inhibitor of P-gp. Objective: In this study, the synthesis of a series of derivatives had been carried out by bioisosterism design on the basis of Dimethyl Cardamonin (DMC). Subsequently, we evaluated their reversal activities as potential P-glycoprotein (P-gp)-mediated Multidrug Resistance (MDR) agents. Methods: Dimethyl cardamonin derivatives were synthesized from acetophenones and the corresponding benzaldehydes in the presence of 40% KOH by Claisen-Schmidt reaction. Their cytotoxicity and reversal activities in vitro were assessed with MTT. Moreover, the compound B4 was evaluated by Doxorubicin (DOX) accumulation, Western blot and wound-healing assays deeply. Results and Discussion: The results showed that compounds B2, B4 and B6 had the potency of MDR reversers with little intrinsic cytotoxicity. Meanwhile, these compounds also demonstrated the capability to inhibit MCF-7 and MCF-7/DOX cells migration. Besides, the most compound B4 was selected for further study, which promoted the accumulation of DOX in MCF-7/DOX cells and inhibited the expressionof P-gp at protein levels. Conclusion: The above findings may provide new insights for the research and development of P-gp-mediated MDR reversal agents.

Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation

Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2′-hydroxy-4′,6′-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC50 = 6.4 μM) with the lowest cytotoxicity (IC50 > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.

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.

Synthesis of flavokawain analogues and their anti-neoplastic effects on drug-resistant cancer cells through Hsp90 inhibition

Hsp90 is an ubiquitous molecular chaperone protein, which plays an important role in regulating maturation and stabilization of many oncogenic proteins. Due to its potential to simultaneously disable multiple signaling pathways, Hsp90 represents great promise as a therapeutic target of cancer. In this study, we synthesized flavokawain analogues and evaluated their biological activities against drug-resistant cancer cells. The study indicated that compound 1i impaired the growth of gefitinib-resistant non-small cell lung cancer (H1975), down-regulated the expression of Hsp90 client proteins including EGFR, Her2, Met, Akt and Cdk4, and upregulated the expression of Hsp70. The result strongly suggested that compound 1i inhibited the proliferation of cancer cells through Hsp90 inhibition. Overall, compound 1i could serve as a potential lead compound to overcome the drug resistance in cancer chemotherapy.

Synthesis, cytotoxicity, and antioxidative activity of minor prenylated chalcones from Humulus lupulus

The minor hop (Humulus lupulus) chalcones 3′-geranylchalconaringenin (3), 5′-prenylxanthohuraol (4), flavokawin (5), xanthohumol H (8), xanthohumol C (9), and 1″,2″-dihydroxanthohumol C (10) were synthesized. The non-natural chalcones 3′-geranyl-6′-O- methylchalconaringenin (2), 3′-methylflavokawin (6), and 2′-0-methyl-3′-prenylchalconaringenin (7) were also synthesized. Cytotoxicity was investigated in HeLa cells, and these compounds all had IC 50 values comparable to xanthohumol (8.2-19.2 μM). The ORAC-fluorescein assay revealed potent antioxidative activity for 7 and 8 with 5.2 and 4.8 Trolox equivalents, respectively.

Insect antifeedant flavonoids from Gnaphalium affine D. Don

The antifeedant flavonoids, 5-hydroxy-3,6,7,8,4'-pentamethoxyflavone (1), 5-hydroxy-3,6,7,8-tetramethoxyflavone (2), 5,6-dihydroxy-3,7- dimethoxyflavone (3), and 4,4',6'-trihydroxy-2'-methoxychalcone (4), have been isolated from cudweed Gnaphalium affine D. Don (Compositae). Four natural flavonoids showed insect antifeedant activity against the common cutworm (Spodoptera litura F.). These flavonoids were detected in small amounts in the plant by HPLC analysis, but these natural compounds had strong antifeedant activity against the common cutworm. On the other hand, 4 was detected in a large amount in the plant, but this compound had only a slight activity. Therefore, these natural compounds were regarded as one of the plant's defensive systems against phytophagous insects along with the woolly plant surface. As for the structure-activity relationship, it is an advantage for antifeedant activity to have no oxy-substituents on the B-ring of the flavonoid but have an ether linkage such as a pyran in the chemical structure.