22609-52-5Relevant academic research and scientific papers
Design, synthesis and apoptosis inducing activity of nonsteroidal flavone-methanesulfonate derivatives on MCF-7 cell line as potential sulfatase inhibitor
Javadi, Mahdiyeh H. S.,Iraji, Aida,Safavi, Maliheh,Montazeri, Hamed,Tarighi, Parastoo,Eftekhari, Samane,Navidpour, Latifeh,Mirfazli, Seyedeh Sara
, p. 1677 - 1687 (2021/07/26)
In recent years, focusing on new potent anticancer agents with selective activity is one of the greatest challenges in cancer therapy. Breast cancer is the most common cancer and the main cause of cancer deaths in women. The sulfatase enzyme plays an important role in converting the sulfated steroids into non-sulfate steroid hormones, which increases the growth and development of many hormone-dependent cancers, such as breast cancer. In this regard, structure-based optimization was conducted to design novel flavone-sulfonates pharmacophore as a new steroid sulfatase inhibitor. In the present work, the conventional methods for the synthesis of 4-oxo-2-phenyl-4H-chromen-7-yl methanesulfonate derivatives were reported. Their cytotoxicity was evaluated with MTT assay against a breast cancer cell line (MCF-7). The apoptosis inducing activity of the most cytotoxic compound 3c with an IC50 value of 0.615 μM was evaluated in comparison to docetaxel in the presence of estradiol which is a crucial growth factor to survive the cancerous cells. The results of double staining Annexin V-FITC/PI analysis suggested that the cytotoxic activity of this compound 3c in MCF-7 cells occurs via apoptosis. Molecular docking studies were conducted to clarify the inhibition mode of the most promising compound (3c) over the sulfatase (1P49) binding site. The analysis revealed the role of hydrogen bond interaction with Gly181 and hydrophobic interactions through the 1P49 active site in the ligand-receptor complex as significant descriptors to rationalize the potential inhibition activity. [Figure not available: see fulltext.]
Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
Abdpour, Shahin,Jalili-Baleh, Leili,Nadri, Hamid,Forootanfar, Hamid,Bukhari, Syed Nasir Abbas,Ramazani, Ali,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Khoobi, Mehdi
, (2021/03/14)
A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8–0.71 μM) and showed remarkable BuChE inhibition activity (IC50 = 1.9–0.006 μM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 μM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 μM) and BuChE (IC50 = 0.006 μM), respectively. The ligand–protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced.neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation
Liu, Honghui,Wang, Yan,Lv, Mingxia,Luo, Yi,Liu, Bu-Ming,Huang, Yan,Wang, Mian,Wang, Jianyi
, (2020/10/23)
A series of novel flavonoid analogues were designed and synthesized. The aimed compounds for urease inhibitory activities were clearly superior to the control drug thiourea (more than 10 times). Among these compounds, L2 (IC50 = 1.343 μM) and L12 (IC50 = 1.207 μM) exhibited the most excellent urease inhibitory activity in vitro. The molecular dockings of L2, L12 and L22 into urease were performed to explore the binding modes and their structure-activity relationship. Furthermore, these aimed compounds showed good druggable properties.
An Efficient One-Pot Synthesis and Anticancer Activity of 4'-Substituted Flavonoids
Wang,Liu,Zhang
, p. 1036 - 1041 (2018/07/06)
A number of 4'-substituted (R = H, Me, Cl, F) flavone derivatives is synthesized from 2-hydroxyacetophenones using the modified Baker–Venkataraman reaction. Compound [3-(4-fluorobenzoyl)-5- hydroxy-4'-fluoroflavone] was synthesized for the first time with the yield of 12%. Antiproliferative assays indicate that the synthesized flavones with F substituent at the 4' position demonstrate higher activity than the other flavone derivatives, particularly against HeLa and MCF-7 with the IC50 9.5 and 2.7 μM, respectively.
Synthesis and antiproliferative activity of some dihydro-1 H-furo[2,3-c]pyrazole-Flavone hybrids
Tangeti, Venkata Swamy,Vasundhara,Satyanarayana,Pavan Kumar, Kaja Srinivas
, p. 1525 - 1532 (2017/05/29)
A new series of dihydro-1 H-furo[2,3-c]pyrazole-flavone hybrids were synthesized from one-pot four-component reaction of β-keto ester (1), hydrazine (2),7-hydroxy 8-formyl flavones (3), pyridiniumylide (4) in presence of NEt3 as catalyst under ethanol reflux conditions and their antiproliferative properties were evaluated against human cancer cell lines, namely, laryngeal carcinoma (Hep2), lung adenocarcinoma (A549) and cervical cancer (HeLa). The best among them, furo[2,3-c]pyrazole-flavone with C4′-methoxy substitution was selected for further structure activity relationship (SAR) studies. Among the derivatives, (4S,5S)-ethyl 4-(7-hydroxy-5-methoxy-4-oxo-2-(2,4,6-trimethoxyphenyl)-4H-chromen-8-yl)-3-methyl-4,5-dihydro-1 H-furo[2,3-c]pyrazole-5-carboxylate (8r) showed most potent cytotoxic activity against all three cancer cell lines. Toxicity studies revealed that the dihydro-1H-furo[2,3-c]pyrazole-flavones are specifically target the cancer cell lines.
Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities
Luo, Wen,Chen, Ying,Wang, Ting,Hong, Chen,Chang, Li-Ping,Chang, Cong-Cong,Yang, Ya-Cheng,Xie, Song-Qiang,Wang, Chao-Jie
, p. 672 - 680 (2016/02/09)
A novel series of 7-aminoalkyl-substituted flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential cholinesterase inhibitors. The results showed that most of the synthesized compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities at the micromolar range. Compound 2-(naphthalen-1-yl)-7-(8-(pyrrolidin-1-yl)octyloxy)-4H-chromen-4-one (5q) showed the best inhibitory activity (IC50, 0.64 μM for AChE and 0.42 μM for BChE) which were better than our previously reported compounds and the commercially available cholinergic agent Rivastigmine. The results from a Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5q with AChE and BChE. Furthermore, molecular modeling study showed that 5q targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, these compounds (5a-5r) did not affect PC12 and HepG2 cell viability at the concentration of 10 μM. Consequently, these flavonoid derivatives should be further investigated as multipotent agents for the treatment of Alzheimer's disease.
Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease
Li, Su-Yi,Wang, Xiao-Bing,Xie, Sai-Sai,Jiang, Neng,Wang, Kelvin D.G.,Yao, He-Quan,Sun, Hong-Bin,Kong, Ling-Yi
, p. 632 - 646 (2013/10/22)
A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-β (Aβ1-42) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Aβ1-42 aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.
An efficient one-pot synthesis of flavones
Chee, Chin Fei,Buckle, Michael J.C.,Rahman, Noorsaadah Abd.
supporting information; experimental part, p. 3120 - 3123 (2011/06/26)
Flavones were prepared using a one-pot procedure starting from the corresponding 2′-hydroxyacetophenones. The latter were treated with 3 equiv of aroyl chloride in wet K2CO3/acetone (1% w/w water) to afford a good yield of flavone and a smaller amount of 3-aroylflavone. Evidence was obtained that the reaction proceeds via a triketone intermediate. When the reactants were heated in 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and pyridine, the 3-aroylflavone was obtained exclusively. Use of a stoichiometric amount of aroyl chloride afforded only the corresponding flavone.
Design, synthesis and biological evaluation of new arylpiperazine derivatives bearing a flavone moiety as α1-adrenoceptor antagonists
Jin, Jing,Wang, Xiao-Bing,Kong, Ling-Yi
scheme or table, p. 909 - 911 (2011/03/20)
Elaborate study on the three-dimensional model of α1- adrenoceptor (α1-AR) antagonists led to the development of a series of new arylpiperazine derivatives bearing a flavone nucleus as α1-AR antagonists. The in vitro activities were evaluated and compounds 1, 4, 10, 13 and 15 showed activities close to the reference compound (Prazosin).
Synthesis of flavonoid 7-O-β-D-glycosides by phase transfer catalysis
Wu, Zheng,Jiang, Ling,Chen, He,Wang, Qiu-An
experimental part, p. 195 - 197 (2009/11/30)
Six flavonoid 7-O-β-D-glycosides 1a-3a and 1b-3b were synthesised from the flavones 7a and 7b by glycosidation and deacetylation with the corresponding a-acetylglycosyl bromides. 7a and 7b were prepared in high yield by an improved Baker-Venkataraman rearrangement using 2, 4- dihydro×yacetophenone as starting material and tetrabutylammonium bromide (TBAB) as a phase transfer catalyst. The glycosidation procedure was modified by using anhydrous K2CO3 in a solvent mixture of DMF/acetone (3:2v/v) and TBAB as a phase transfer catalyst.
