404597-94-0

Upstream product

• 108-73-6 3,5-dihydroxyphenol 
• 65490-09-7 2'-hydroxy-4',6'-bis(methoxymethoxy)acetophenone 
• 77-78-1 dimethyl sulfate 
• 74-88-4 methyl iodide 
• 480-66-0 2,4,6-trihydroxyacetophenone 
• 3602-54-8 4,6-dihydroxy-2-methoxyacetophenone 
• 107-30-2 chloromethyl methyl ether 

Downstream Products

• 1082076-62-7 (2E)-1-(2,4-di(methoxymethoxy)-6-methoxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one 
• 1013662-04-8 (E)-1-(2-methoxy-4,6-bis(methoxymethoxy)phenyl)-3-phenylprop-2-en-1-one 
• 1620631-18-6 (2E,2'E)-1,1'-[methylenebis(2,4-dihydroxy-6-methoxy-3,1-phenylene)]bis(3-phenylprop-2-en-1-one) 
• 62014-87-3 helichrysetin 
• 1207843-49-9 (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-(4-methylphenyl)-2-propen-1-one 
• 1207843-45-5 (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-(3-methoxy-4-hydroxyphenyl)-2-propen-1-one 
• 1207843-46-6 (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-(3,4,5-trimethoxyphenyl)-2-propen-1-one 
• 1034276-32-8 (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-(3,4-dihydroxyphenyl)-2-propen-1-one 
• 1207843-42-2 (2E)-3-(4-chlorophenyl)-1-(2,4-dihydroxy-6-methoxyphenyl)-2-propen-1-one 
• 1207843-41-1 (2E)-1-(2,4-dihydroxy-6-methoxyphenyl)-3-[4-(trifluoromethyl)phenyl]-2-propen-1-one 

Relevant academic research and scientific papers

Discovery of flavonoids from scutellaria baicalensis with inhibitory activity against PCSK 9 expression: Isolation, synthesis and their biological evaluation

Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cell

Neuroregenerative Potential of Prenyl- And Pyranochalcones: A Structure-Activity Study

Loss of neuronal tissue is a hallmark of age-related neurodegenerative diseases. Since adult neurogenesis has been confirmed in the human brain, great interest has arisen in substances stimulating the endogenous neuronal regeneration mechanism based on ad

Polymethoxy flavone derivative with anti-hepatitis A virus activity as well as preparation method and application of polymethoxy flavone derivative

The invention belongs to the field of medicinal chemistry, and relates to a polymethoxy flavone derivative with anti-hepatitis A virus activity as well as a preparation method and application of the polymethoxy flavone derivative. The polymethoxylated fla

New methods to assess 6-thiopurine toxicity and expanding its therapeutic application to pancreatic cancer via small molecule potentiators

6-Thiopurine (6TP) is a potent cytotoxic agent that is a clinically prescribed anti-metabolite employed in the treatment of numerous blood cancers since 1952. However, its reported severe toxicities limit its general usage in the clinic. We previously have undertaken investigations into identifying the mode of toxicity for 6TP, and have found that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU), is responsible for the in vitro inhibition of UDP-glucose dehydrogenase (UDPGDH) in a UV-vis method. In this method, inhibition was quantified through the quantification of NADH production, however, purines absorb at the same wavelength and thereby can interfere with the NADH detection. Herein, we report a HPLC method that allows for direct quantification of UDP-glucuronic acid, product from UDPGDH, for the assessment of inhibition towards UDPGDH with no interference from purines. In this method it was revealed that 6TP possesses a greater inhibitory properties than previously observed; 111 vs. 288 μM. Building upon the data collected from a previously performed rat hepatocyte study, which correlated our in vitro to in vivo inhibition theories about UDPGDH, we have developed a bio-mimic in vitro assay to aid in the inhibitory assessment of 6TP and analogs. In our efforts to expand the use of 6TP, and analogs constructed, our laboratory has undertaken a screening campaign to identify small molecule potentiators that work in synergy with 6TP in other types of cancers. Three chalcone-based compounds have been discovered through our total synthesis campaign of uvaretin, and it has been found that 11c has strong synergism with 6TP in the pancreatic cancer cell line MIA PaCa-2. Through the work presented herein, we reveal new methods to assess toxicity of 6TP and future analogs and new small molecules that work in synergy to expand the therapeutic applications of this neglected cytotoxic agent.

The winding road of the uvaretin class of natural products: From total synthesis to bioactive agent discovery

Herein, we disclose the development of a synthetic route to gain access to the uvaretin class of chalcone natural products. In this, the construction of a small library was achieved, and the collection was evaluated for cytotoxicity and other biological properties. Uvaretin (1) was accessed via a seven-step route in an overall yield of 15.1%. Within this route, the unsaturated enone variant of uvaretin (2), also a natural product, was accessed in a 16.7% yield over six steps. This route provides a nearly three-fold increase in yields of 1 and 2 in comparison to the previous synthetic route accessing them in 5.8% and 3.0% overall yields, respectively. Evaluation of 1 and 2 revealed IC50 values between 2.0 and 5.1 μM in the cancerous cell lines HeLa, U937, A549, and MIA PaCa-2. Screening of the whole chalcone library set led to the discovery of over 30 compounds, within six cancerous cell lines, possessing single digit μM IC50 activity as sole agents. Furthermore, multiple library members were found to possess promising potentiating properties with known chemotherapeutic agents.

Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent

The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 μM). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.

Facile formation of methylenebis(chalcone)s through unprecedented methylenation reaction. Application to antiparasitic and natural product synthesis

The formation of methylenebis(chalcone)s has been discovered during deprotection with methoxymethyl groups from trihydroxychalcones. Studies on this methylenation reaction led to a mechanism hypothesis that was extended to other chalcones and to dihydrochalcone, acetophenone, benzophenone and flavone derivatives. This new method was applied to the rapid synthesis of natural product piperanduncin C. These original methylenebis compounds were also evaluated for their antiparasitic activity. Copyright

Construction of 2-substituted-3-functionalized benzofurans via intramolecular heck coupling: Application to enantioselective total synthesis of daphnodorin B

A novel approach was developed for the synthesis of 2-substituted-3- functionalized benzofurans, using an intramolecular Heck reaction which was further applied in the first enantioselective total synthesis of Daphnodorin B.

In vitro and in vivo anti-Leishmania activity of polysubstituted synthetic chalcones

The in vitro screening of 43 polysubstituted chalcones against Leishmania amazonensis axenic amastigotes, led to the evaluation of 9 of them in a macrophage-infected model with the two other most infectious Leishmania species prevalent in Peru (L. braziliensis and L. peruviana). The five most active and selective chalcones were studied in vivo, resulting on the identification of two chalcones with high reduction parasite burden percentages.

Natural and non-natural prenylated chalcones: Synthesis, cytotoxicity and anti-oxidative activity

A general strategy for the synthesis of 3′-prenylated chalcones was established and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2), xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated chalcones was investigated in a HeLa cell line and revealed that non-natural prenylated chalcones, like 2′,3,4′,5-tetrahydroxy-6′-methoxy-3′-prenylchalcone (9, IC50 3.2 ± 0.4 μM) as well as the phase 1 metabolite of xanthohumol (1), 3-hydroxyxanthohumol (8, IC50 2.5 ± 0.5 μM), were more active in comparison to 1 (IC50 9.4 ± 1.4 μM). A comparison of the cytotoxic activity of xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs helichrysetin (12, IC50 5.2 ± 0.8) and 3-hydroxyhelichrysetin (13, IC50 14.8 ± 2.1) showed that the prenyl side chain at C-3′ has an influence on the cytotoxicity against HeLa cells only for the dihydroxylated derivative. This offers interesting synthetic possibilities for the development of more potent compounds. The ORAC activity of the synthesized compounds was also investigated and revealed the highest activity for compounds 12, 4′-methylxanthohumol (4), and desmethylxanthohumol (2), with 4.4 ± 0.6, 3.8 ± 0.4, and 3.8 ± 0.5 Trolox equivalents, respectively.