94103-36-3Relevant articles and documents
Synthesis and Evaluation of the Acetylcholinesterase Inhibitory Activities of Some Flavonoids Derived from Naringenin
Cao, Thi-Cam-Nhung,Tran, Thai-Son,Tran, The-Huan,Vo, Thi-Quynh-Nhi,Vo, Thi-Thu-Hien
, (2021/12/27)
Alzheimer's disease (AD) is an irreversible neurodegenerative disease that affects many older people adversely. AD has been putting a huge socioeconomic burden on the healthcare systems of many developed countries with aging populations. The need for new therapies that can halt or reverse the progression of the disease is now extremely great. A research approach in the finding new treatment for AD that has attracted much interest from scientists for a long time is the reestablishment of cholinergic transmission through inhibition of acetylcholinesterase (AChE). Naringenin is a flavonoid with the potential inhibitory activity against AChE. From naringenin, many other flavonoid derivatives, such as flavanones and chalcones, can be synthesized. In this study, by applying the Williamson method, nine flavonoid derivatives were synthesized, including four flavanones and five chalcones. The evaluation of AChE inhibitory activity by the Ellman method showed that there were four substances (2, 4, 5, and 7) with relatively good biological activities (IC50 100 μM), and these biological activities were better than that of naringenin. The molecular docking revealed that strong interactions with amino acid residue Ser200 of the catalytic triad and those of the peripheral region of the enzyme were crucial for strong effects against AChE. Compound 7 had the strongest AChE inhibitory activity (IC50 13.0 ± 1.9 μM). This substance could be used for further studies.
Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives
Thieury, Charlotte,Lebouvier, Nicolas,Le Guével, Rémy,Barguil, Yann,Herbette, Ga?tan,Antheaume, Cyril,Hnawia, Edouard,Asakawa, Yoshinori,Nour, Mohammed,Guillaudeux, Thierry
, p. 1817 - 1829 (2017/03/08)
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.
ANTI-INVASIVE COMPOUNDS
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Paragraph 0361-0363; 0369-0372, (2015/02/18)
The present invention relates to the field of anti-invasive compounds and methods for predicting the anti-invasive activity of said compounds, as well as their use in the prevention and/or treatment of diseases associated with undesired cell invasion; in particular, this invention relates to the field of anti-invasive chalcone-like compounds.
Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent
Zhang, Baoxin,Duan, Dongzhu,Ge, Chunpo,Yao, Juan,Liu, Yaping,Li, Xinming,Fang, Jianguo
supporting information, p. 1795 - 1805 (2015/04/27)
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.
4-Fluoro-3′,4′,5′-trimethoxychalcone as a new anti-invasive agent. From discovery to initial validation in an in vivo metastasis model
Roman, Bart I.,De Ryck, Tine,Patronov, Atanas,Slavov, Svetoslav H.,Vanhoecke, Barbara W.A.,Katritzky, Alan R.,Bracke, Marc E.,Stevens, Christian V.
supporting information, p. 627 - 639 (2015/08/03)
Invasion and metastasis are responsible for 90% of cancer-related mortality. Herein, we report on our quest for novel, clinically relevant inhibitors of local invasion, based on a broad screen of natural products in a phenotypic assay. Starting from micromolar chalcone hits, a predictive QSAR model for diaryl propenones was developed, and synthetic analogues with a 100-fold increase in potency were obtained. Two nanomolar hits underwent efficacy validation and eADMET profiling; one compound was shown to increase the survival time in an artificial metastasis model in nude mice. Although the molecular mechanism(s) by which these substances mediate efficacy remain(s) unrevealed, we were able to eliminate the major targets commonly associated with antineoplastic chalcones.
Trimethoxy-chalcone derivatives inhibit growth of Leishmania braziliensis: Synthesis, biological evaluation, molecular modeling and structure-activity relationship (SAR)
Bello, Murilo Lamim,Chiaradia, Louise Domeneghini,Dias, Luiza Rosaria Sousa,Pacheco, Leticia Kramer,Stumpf, Taisa Regina,Mascarello, Alessandra,Steindel, Mario,Yunes, Rosendo Augusto,Castro, Helena Carla,Nunes, Ricardo Jose,Rodrigues, Carlos Rangel
, p. 5046 - 5052 (2011/09/30)
In this work we described the synthesis, the antileishmanial activity and the molecular modeling and structure-activity relationship (SAR) evaluations of a series of chalcone derivatives. Among these compounds, the methoxychalcones 2h, 2i, 2j, 2k and 2l showed significant antileishmanial activity (IC 50 50 = 2.7 μM), 2j (IC50 = 3.9 μM) and 2k (IC50 = 4.6 μM) derivatives presented better antileishmanial activity than the control drug pentamidine (IC50 = 6.0 μM). Our SAR study showed the importance of methoxy di-ortho substitution at phenyl ring A and the relationship between the frontier orbital HOMO coefficients distribution of these molecules and their activity. The most active compounds 2h, 2i, 2j, 2k, and 2l fulfilled the Lipinski rule-of-five which theoretically is important for good drug absorption and permeation through biological membranes. The potential profile of 2j (IC 50 = 3.9 μM and CC50 = 216 μM) pointed this chalcone derivative as a hit compound to be further explored in antileishmanial drug design.
Synthesis and pharmacological activity of chalcones derived from 2,4,6-trimethoxyacetophenone in RAW 264.7 cells stimulated by LPS: Quantitative structure-activity relationships
Chiaradia, Louise Domeneghini,dos Santos, Rodrigo,Vitor, Carlos Eduardo,Vieira, Andre Alexandre,Leal, Paulo Cesar,Nunes, Ricardo Jose,Calixto, Joao Batista,Yunes, Rosendo Augusto
, p. 658 - 667 (2008/09/17)
Inhibition of nitric oxide (NO) production by altering the expression of induced enzymes involved is potentially an important strategy for obtaining antiinflammatory agents. In the search for hits to obtain lead compounds for new drugs of this class, 14 s
Total synthesis of kaempferol and methylated kaempferol derivatives
Lee, Yean-Jang,Wu, Tsao-Dong
, p. 201 - 206 (2007/10/03)
Kaempferol (1), a natural product from various plants, was synthesized in which the longest linear sequence is only seven steps in overall yields of 47% from commercially available 1,3,5-trimethoxybenzene (10). The methylated kaempferols 2-5 were also prepared by use of this concise synthetic methodology. The key transformations in this synthesis involved the I2 oxidative-promoting-cyclization and DDO oxidative hydroxylation. Several strategies to achieve 1 are provided.
Insect antifeedant flavonoids from Gnaphalium affine D. Don
Morimoto, Masanori,Kumeda, Sumiko,Komai, Koichiro
, p. 1888 - 1891 (2007/10/03)
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.
