552-41-0Relevant articles and documents
Synthesis, vibrational, NMR, quantum chemical and structure-activity relation studies of 2-hydroxy-4-methoxyacetophenone
Arjunan,Devi,Subbalakshmi,Rani,Mohan
, p. 164 - 177 (2014)
The stable geometry of 2-hydroxy-4-methoxyacetophenone is optimised by DFT/B3LYP method with 6-311++G* and cc-pVTZ basis sets. The structural parameters, thermodynamic properties and vibrational frequencies of the optimised geometry have been determined. The effects of substituents (hydroxyl, methoxy and acetyl groups) on the benzene ring vibrational frequencies are analysed. The vibrational frequencies of the fundamental modes of 2-hydroxy-4-methoxyacetophenone have been precisely assigned and analysed and the theoretical results are compared with the experimental vibrations. 1H and 13C NMR isotropic chemical shifts are calculated and assignments made are compared with the experimental values. The energies of important MO's, the total electron density and electrostatic potential of the compound are determined. Various reactivity and selectivity descriptors such as chemical hardness, chemical potential, softness, electrophilicity, nucleophilicity and the appropriate local quantities are calculated.
Synthesis of novel isoflavone/benzo-δ-sultam hybrids as potential anti-inflammatory drugs
Mengheres, Gabriel,Rice, Craig R.,Olajide, Olumayokun A.,Hemming, Karl
supporting information, (2021/01/12)
A small series of novel isoflavone/benzo-δ-sultam hybrids was synthesised and evaluated as potential anti-inflammatory and neuroprotective drugs in LPS-activated BV2 microglia. The benzo-δ-sultam core was constructed in a two-step reaction by coupling 2-halobenzenesulfonamide derivatives with terminal alkynes, followed by a 6-endo-dig cyclisation. The synthesised compounds, including precursors and hybrids, were tested for their ability to inhibit NO and TNF-α production in LPS-stimulated BV2 microglial cells, and the results are promising. The most potent hybrid reduces the NO production to 41%, and the TNF-α to 34% at 20 μM final concentration in the well.
Design, synthesis and evaluation of novel dimethylamino chalcone-O-alkylamines derivatives as potential multifunctional agents against Alzheimer's disease
Sang, Zhipei,Song, Qing,Cao, Zhongcheng,Deng, Yong,Tan, Zhenghuai,Zhang, Li
, (2021/03/04)
A novel series of dimethylamino chalcone-O-alkylamines derivatives was designed and synthesized as multifunctional agents for the treatment of AD. All the target compounds exhibited significant abilities to inhibit and disaggregate Aβ aggregation, and acted as potential selective AChE inhibitors, biometal chelators and selective MAO-B inhibitors. Among these compounds, compound TM-6 showed the greatest inhibitory activity against self-induced Aβ aggregation (IC50 = 0.88 μM) and well disaggregation ability toward self-induced Aβ aggregation (95.1%, 25 μM), the TEM images, molecular docking study and molecular dynamics simulations provided reasonable explanation for its high efficiency, and it was also found to be a remarkable antioxidant (ORAC-FL values of 2.1eq.), the best AChE inhibitor (IC50 = 0.13 μM) and MAO-B inhibitor (IC50 = 1.0 μM), as well as a good neuroprotectant. UV–visual spectrometry and ThT fluorescence assay revealed that compound TM-6 was not only a good biometal chelator by inhibiting Cu2+-induced Aβ aggregation (95.3%, 25 μM) but also could disassemble the well-structured Aβ fibrils (88.1%, 25 μM). Further, TM-6 could cross the blood-brain barrier (BBB) in vitro. More importantly, compound TM-6 did not show any acute toxicity in mice at doses of up to 1000 mg/kg and improved scopolamine-induced memory impairment. Taken together, these data indicated that TM-6, an excellent balanced multifunctional inhibitor, was a potential lead compound for the treatment of AD.
Anti‐melanogenic properties of velutin and its analogs?
Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
, (2021/06/03)
Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors
Albi?ana, Carlos Berenguer,Brynda, Ji?í,Fanfrlík, Jind?ich,Flieger, Miroslav,Hodek, Jan,Karlukova, Elena,Ko?í?ek, Milan,Konvalinka, Jan,Machara, Ale?,Majer, Pavel,Radilová, Kate?ina,Weber, Jan,Zima, Václav
supporting information, (2020/09/09)
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.
Ferulin C triggers potent PAK1 and p21-mediated anti-tumor effects in breast cancer by inhibiting Tubulin polymerization in vitro and in vivo
He, Zhendan,Huang, Jian,Pan, Dabo,Wang, Jinhui,Yao, Dahong,Zhang, Jin,Zhen, Yongqi
, (2019/12/26)
Ferulin C, a natural sesquiterpene coumarin, isolated from the roots of Ferula ferulaeoides (Steud.) Korov, displaying potent antiproliferatory activity against breast cancer cells. This study aimed to elucidate the underlying molecular mechanisms of Ferulin C-induced breast cancer cells death in vitro and in vivo. Ferulin C presented potent antiproliferatory activity against MCF-7 and MDA-MB-231 cells and remarkable tubulin polymerization inhibitory activity (IC50 = 9.2 μM). Meanwhile, we predicted Ferulin C bind to the Colchicine site of tubulin through CETSA assay, molecular docking and molecular dynamics (MD) simulations. In immunofluorescence assay, Ferulin C disturbed the microtubule integrity and structure. Furthermore, Ferulin C stimulated significant cell cycle arrest in the G1/S period via p21Cip1/Waf1 - CDK2 signaling, induced classic cell apoptosis, impaired metastasis via down-regulating Ras-Raf-ERK and AKT-mTOR signaling. Intriguingly, Ferulin C treatment induced autophagy by ULK1 signaling to synergize with the inhibition of proliferation and metastasis. Based upon the RNAseq analysis, PAK1, as a novel essential modulator, was involved in the signaling regulated by Ferulin C -induced α/β-tubulin depolymerization. Additionally, Ferulin C displayed an acceptable antiproliferatory activity in an MCF-7 xenograft model without inducing obvious weight loss in the Ferulin C treated mice. Summarily, our findings substantiated that Ferulin C was a potent, colchicine site binding microtubule-destabilizing agent with anti-proliferation and anti-metastasis activity via PAK1 and p21-mediated signaling in breast cancer cells.
Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N, N-Dimethylformamide Dimethyl Acetal
Sang, Dayong,Yue, Huaxin,Zhao, Zhengdong,Yang, Pengtao,Tian, Juan
, p. 6429 - 6440 (2020/07/14)
Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.
Selective ether bond breaking method of aryl alkyl ether
-
Paragraph 0181-0185, (2020/09/16)
The invention discloses a selective aryl alkyl ether cracking method, which comprises that aryl alkyl ether, aluminum iodide and an additive are subjected to a selective ether bond cleavage reaction in an organic solvent at a temperature of -20 DEG C to a reflux temperature to generate phenol and derivatives thereof. The method is mild in condition and simple and convenient to operate, is suitablefor cracking aryl alkyl ether containing o-hydroxyl and o-carbonyl and acetal ether, and can also be used for removing tertiary carbon hydroxyl protecting groups with higher steric hindrance, such astriphenylmethyl, tertiary butyl and the like.
Design, synthesis and QSAR study of 2′-hydroxy-4′-alkoxy chalcone derivatives that exert cytotoxic activity by the mitochondrial apoptotic pathway
Marquina, Silvia,Maldonado-Santiago, Maritza,Sánchez-Carranza, Jessica Nayelli,Antúnez-Mojica, Mayra,González-Maya, Leticia,Razo-Hernández, Rodrigo Said,Alvarez, Laura
, p. 43 - 54 (2018/11/27)
Eleven 4′-alkoxy chalcones were synthesized and biologically evaluated for their antiproliferative activity against four human tumor cell lines (PC-3, MCF-7, HF-6, and CaSki). Compounds 3a-3d and 3f were selective against PC-3, with IC50 values ranging from 8.08 to 13.75 μM. In addition, chalcones 3a-3c did not affect the normal fibroblasts BJ cells. The most active and selective compounds were further evaluated for their effect on the progression of cell cycle in PC-3 cells, and chalcones 3a and 3c induced a G2/M phase arrest. Furthermore, it was found that these three chalcones induced the mitochondrial apoptotic pathway by regulating Bax and Bcl-2 transcripts and by increasing caspase 3/7 activation. Otherwise, the QSAR model indicates that the double bond of the α,β-unsaturated carbonyl, as well as the planar structure geometry, are important to the biological activity of the synthetized chalcones. Based on these studies, it was concluded that withdrawing substituents in ring A, decrease the antiproliferative activity. This is related to the possible mechanism of action of these compounds, where a Michael addition needs to take place in order to be a potent anticancer agent.
A molybdenum based metallomicellar catalyst for controlled and chemoselective oxidation of activated alcohols in aqueous medium
Thiruvengetam, Prabaharan,Chakravarthy, Rajan Deepan,Chand, Dillip Kumar
, p. 123 - 133 (2019/07/19)
A surfactant based oxodiperoxo molybdenum complex, which could activate molecular oxygen, has been employed as a catalyst for controlled oxidation of benzylic alcohols to corresponding carbonyls. The oxidation reactions were carried out under aqueous environment, however, in the absence of any extraneous base or co-catalyst. Sensitive/oxidizable functional groups like cyano, sulfide, hydroxyl, aryl-hydroxyl, alkene (internal/terminal), alkyne (internal/terminal), and acetal were tolerated during the transformations. Such selectivity is attributed to the mild nature of the catalyst. The methodology could also be scaled-up for multi-gram synthesis and the protocol is likely to find practical use since it requires an inexpensive recyclable-catalyst and easily available oxidant (under green conditions). A plausible mechanism is proposed with the help of preliminary computational study.
