- Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
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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.
- Abdpour, Shahin,Jalili-Baleh, Leili,Nadri, Hamid,Forootanfar, Hamid,Bukhari, Syed Nasir Abbas,Ramazani, Ali,Ebrahimi, Seyed Esmaeil Sadat,Foroumadi, Alireza,Khoobi, Mehdi
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- Identification of inhibitors targeting polyketide synthase 13 of Mycobacterium tuberculosis as antituberculosis drug leads
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Polyketide synthase 13 (Pks13) is an essential enzyme in the synthesis of mycolic acids in Mtb. Therefore, Pks13 is a promising drug target for tuberculosis treatment. We used a structure-guided approach to identify novel chemotype inhibitors of Pks13 and assessed them using a Pks13 enzymatic assay and surface plasmon resonance. The structure–activity relationships (SAR) results demonstrated that the substituents at the 2, 5, and 6 positions of the 4H-chromen-4-one scaffold are critical for maintaining the MIC. Compound 6e with 2-hydroxyphenyl at the 2 position of the 4H-chromen-4-one scaffold, exhibited potent activity against Mtb H37Rv (MIC = 0.45 μg/mL) and displayed good Pks13 affinity and inhibition (IC50 = 14.3 μM). This study described here could provide an avenue to explore a novel inhibitor class for Pks13 and aid the further development of antituberculosis drugs.
- Wang, Xiao,Zhao, Wenting,Wang, Bin,Ding, Wei,Guo, Hao,Zhao, Hongyi,Meng, Jianzhou,Liu, Sihan,Lu, Yu,Liu, Yishuang,Zhang, Dongfeng
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- Design, synthesis and apoptosis inducing activity of nonsteroidal flavone-methanesulfonate derivatives on MCF-7 cell line as potential sulfatase inhibitor
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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.]
- Javadi, Mahdiyeh H. S.,Iraji, Aida,Safavi, Maliheh,Montazeri, Hamed,Tarighi, Parastoo,Eftekhari, Samane,Navidpour, Latifeh,Mirfazli, Seyedeh Sara
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p. 1677 - 1687
(2021/07/26)
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- Divergent synthesis of flavones and flavanones from 2′-hydroxydihydrochalconesviapalladium(ii)-catalyzed oxidative cyclization
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Divergent and versatile synthetic routes to flavones and flavanonesviaefficient Pd(ii) catalysis are disclosed. These Pd(ii) catalyses expediently provide a variety of flavones and flavanones from 2′-hydroxydihydrochalcones as common intermediates, depending on oxidants and additives,viadiscriminate oxidative cyclization sequences involving dehydrogenation, respectively, in a highly atom-economic manner.
- Son, Seung Hwan,Cho, Yang Yil,Yoo, Hyung-Seok,Lee, Soo Jin,Kim, Young Min,Jang, Hyu Jeong,Kim, Dong Hwan,Shin, Jeong-Won,Kim, Nam-Jung
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p. 14000 - 14006
(2021/04/22)
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- Flavonoid analogues as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation
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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.
- Liu, Honghui,Wang, Yan,Lv, Mingxia,Luo, Yi,Liu, Bu-Ming,Huang, Yan,Wang, Mian,Wang, Jianyi
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- Nitrogen-containing flavonoid and their analogs with diverse B-ring in acetylcholinesterase and butyrylcholinesterase inhibition
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In this study, a series of new flavones (2-phenyl-chromone), 2-naphthyl chromone, 2-anthryl-chromone, or 2-biphenyl-chromone derivatives containing 6 or 7-substituted tertiary amine side chain were designed, synthesized, and evaluated in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition. The results indicated that the alteration of aromatic ring connecting to chromone scaffold brings about a significant impact on biological activity. Compared with flavones, the inhibitory activity of 2-naphthyl chromone, 2-anthryl-chromone derivatives against AChE significantly decreased, while that of 2-biphenyl chromone derivatives with 7-substituted tertiary amine side chain is better than relative flavones derivatives. For all new synthesized compounds, the position of tertiary amine side chain obviously influenced the activity of inhibiting AChE. The results above provide great worthy information for the further development of new AChE inhibitors. Among the newly synthesized compounds, compound 5a is potent in AChE inhibition (IC50 = 1.29 ± 0.10 μmol/L) with high selectivity for AChE over BChE (selectivity ratio: 27.96). An enzyme kinetic study of compound 5a suggests that it produces a mixed-type inhibitory effect against AChE.
- Lu, Qiao-Qiao,Chen, Ya-Ming,Liu, Hao-Ran,Yan, Jian-Ye,Cui, Pei-Wu,Zhang, Qian-Fan,Gao, Xiao-Hui,Feng, Xing,Liu, Ying-Zi
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p. 1037 - 1047
(2020/08/06)
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- Biocatalytic green alternative to existing hazardous reaction media: Synthesis of chalcone and flavone derivatives via the Claisen-Schmidt reaction at room temperature
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Owing to the increasing amount of waste materials around the globe, the conversion of waste or secondary by-products to value-added products for various applications has gained significant interest. Herein, two novel agro-food waste products, Musa sp. 'Malbhog' peel ash (MMPA) and Musa Champa Hort. ex Hook. F. peel ash (MCPA) are used as catalysts to promote an inexpensive, efficient and eco-friendly carbon-carbon bond forming crossed aldol reaction at room temperature in solvent free conditions. Furthermore, the resulting products were subjected to reactions with these promoters in an oxygen atmosphere and led to the formation of novel flavone derivatives. Moreover, the used catalysts were properly characterized using different sophisticated analytical techniques such as Fourier-transform infrared spectroscopy (FT-IR), X-ray diffractometry (XRD), Brunauer-Emmett-Teller analysis (BET), Raman spectroscopy, scanning electron microscopy energy dispersive X-ray spectroscopy (SEM-EDS), transition electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) along with element detection using atomic absorption spectroscopy and ion chromatographic methods. These two approaches are metal free, as well as being devoid of any extra additives, co-catalysts, harsh conditions, the use of column chromatography for purification and result in a higher yield of the product within a short space of time. The catalytic abilities of the promoter were also examined to synthesize important bioactive molecules such as butein and apigenin at room temperature. With gram scale synthesis of the chalcone derivatives, the used catalysts (MMPA and MCPA) were further reused for five cycles and did not demonstrate any loss in catalytic activity.
- Tamuli, Kashyap J.,Sahoo, Ranjan K.,Bordoloi, Manobjyoti
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supporting information
p. 20956 - 20965
(2020/12/31)
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- Synthesis and biological evaluation of flavone-8-acrylamide derivatives as potential multi-target-directed anti Alzheimer agents and investigation of binding mechanism with acetylcholinesterase
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In a search for novel multifunctional anti-Alzheimer agents, a congeneric set of seventeen flavone-8-acrylamide derivatives (8a─q)were synthesized and evaluated for their cholinesterase inhibitory, antioxidant, neuroprotective and modulation of Aβ aggregation activities. The target compounds showed effective and selective inhibitory activity against the AChE over BuChE. In addition, the target compounds also showed moderate anti-oxidant activity and strong neuroprotective capacities, and accelerated dosage-dependently the Aβ aggregation. Also, we presented here a complete study on the interaction of 8a, 8d, 8e, 8h and 8i with AChE. Through fluorescence emission studies, the binding sites number found to be 1, binding constants were calculated as 2.04 × 104, 2.22 × 104, 1.18 × 104, 9.8 × 103 and 3.2 × 104 M?1 and free energy change as ?5.83, ?5.91, ?5.51, ?5.41 and ?6.12 kcal M?1 at 25 °C which were well agreed with the computational calculations indicating a strong binding affinity of flavones and AChE. Furthermore, the CD studies revealed that the secondary structure of AChE became partly unfolded upon binding with 8a, 8d, 8e, 8h and 8i.
- Shaik, Jeelan Basha,Yeggoni, Daniel Pushparaju,Kandrakonda, Yelamanda Rao,Penumala, Mohan,Zinka, Raveendra Babu,Kotapati, Kasi Viswanath,Darla, Mark Manidhar,Ampasala, Dinakara Rao,Subramanyam, Rajagopal,Amooru, Damu Gangaiah
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- Method for synthesizing 2-aryl benzopyrone flavonoid derivatives
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The invention relates to a method for synthesizing 2-aryl benzopyrone flavonoid derivatives, and relates to a method for synthesizing a compound, the method for synthesizing 2-aryl benzopyrone flavonoid derivatives is suitable for the synthesis of 2-aryl benzopyrone flavonoid derivatives containing different substituents. The method aims to solve the technical problems of low yield, long reactionperiod, and complicated post-treatment and high operation difficulty of the existing synthesis method of the ketone flavonoid derivative. The method comprises the following steps of: 1, preparing beta-propanedione compounds; 2, preparing flavonoid compound 2-aryl benzopyranones. The method completes esterification and rearrangement in one step, which is simple and practical, reduces intermediate links of reaction, saves separation and purification of intermediate products, improves utilization rate of raw materials, reduces reaction temperature, shortens reaction time under microwave radiation, reduces solvent consumption, the post-treatment is relatively simple, the yield is relatively high and no by-products exist, and can also react in the presence of a small amount of water, the reaction is easy to operate, and the method is suitable for industrial production. The method belongs to the technical field of compound synthesis.
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Paragraph 0055; 0058; 0059
(2019/04/30)
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- Microwave-assisted synthesis of novel bis-flavone dimers as new anticancer agents
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In this study, we describe a microwave-based click chemistry method used to prepare a family of novel bis-flavone dimers. The substituted 7-hydroxy and 4’-hydroxy flavonoids were linked through a triazole ring. The compounds were easily synthesized and purified in high yields. The bis-flavonoids were tested on different cell lines including HCT116, HepG2, MCF7 and MOLT-4. Several analogues showed to have anticancer activity with IC50 values in the range of 20-60 μM. Flavonoids are known for their anticancer properties and this method provides the basis for new medicinal structures.
- McGown, Andrew,Ragazzon-Smith, Abby,Hadfield, John A.,Potgetier, Herman,Ragazzon, Patricia A.
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supporting information
p. 66 - 75
(2019/05/04)
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- New Flavone-Cyanoacetamide Hybrids with a Combination of Cholinergic, Antioxidant, Modulation of β-Amyloid Aggregation, and Neuroprotection Properties as Innovative Multifunctional Therapeutic Candidates for Alzheimer's Disease and Unraveling Their Mechanism of Action with Acetylcholinesterase
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In line with the modern multi-target-directed ligand paradigm of Alzheimer's disease (AD), a series of 19 compounds composed of flavone and cyanoacetamide groups have been synthesized and evaluated as multifunctional agents against AD. Biological evaluation demonstrated that compounds 7j, 7n, 7o, 7r, and 7s exhibited excellent inhibitory potency (AChE, IC50 of 0.271 ± 0.012 to 1.006 ± 0.075 μM) and good selectivity toward acetylcholinesterase, significant antioxidant activity, good modulation effects on self-induced Aβ aggregation, low cytotoxicity, and neuroprotection in human neuroblastoma SK-N-SH cells. Further, an inclusive study on the interaction of 7j, 7n, 7o, 7r, and 7s with AChE at physiological pH 7.2 using fluorescence, circular dichroism, and molecular docking methods suggested that these derivatives bind strongly to the peripheral anionic site of AChE mostly through hydrophobic interactions. Overall, the multifunctional profiles and strong AChE binding affinity highlight these compounds as promising prototypes for further pursuit of innovative multifunctional drugs for AD.
- Basha, Shaik Jeelan,Mohan, Penumala,Yeggoni, Daniel Pushparaju,Babu, Zinka Raveendra,Kumar, Palaka Bhagath,Rao, Ampasala Dinakara,Subramanyam, Rajagopal,Damu, Amooru Gangaiah
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p. 2206 - 2223
(2018/05/23)
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- An Efficient One-Pot Synthesis and Anticancer Activity of 4'-Substituted Flavonoids
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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.
- Wang,Liu,Zhang
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p. 1036 - 1041
(2018/07/06)
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- Synthesis and biological evaluation of Complex I inhibitor R419 and its derivatives as anticancer agents in HepG2 cells
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In this study, Complex I inhibitor R419 was firstly revealed to have significant anticancer activity against HepG2 cells (IC50 = 5.2 ± 0.9 μM). Based on this finding, a series of R419 derivatives were synthesized and biologically evaluated. As results, 9 derivatives were found to have obvious anticancer activity. Among them, H20 exhibited the most potent activity (IC50 = 2.8 ± 0.4 μM). Mechanism study revealed that H20 caused severe depletion of cellular ATP, dose-dependently activated AMPK, decreased Bcl-2/Bax ratio and induced necrotic cell death. Most importantly, H20 displayed definite inhibitory activity against Complex I.
- Huang, Yaping,Sun, Geng,Wang, Pengfei,Shi, Rui,Zhang, Yanchun,Wen, Xiaoan,Sun, Hongbin,Chen, Caiping
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supporting information
p. 2957 - 2960
(2018/07/21)
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- Design, synthesis and biological evaluation of 2-Phenyl-4H-chromen-4-one derivatives as polyfunctional compounds against Alzheimer’s disease
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Polyfunctional compounds comprise a novel class of therapeutic agents for the treatment of multi-factorial diseases. A series of 2-Phenyl-4H-chromen-4-one and its derivatives (5a–n) were designed, synthesized, and evaluated for their poly-functionality against acetylcholinestrase (AChE) and advanced glycation end products (AGEs) formation inhibitors against Alzheimer’s disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit AChE AGEs formation with additional radical scavenging activity. Especially, 5m, 5b, and 5j displayed the greatest ability to inhibit AChE (IC50 = 8.0, 8.2, and 11.8 nM, respectively) and AGEs formation (IC50 = 55, 79, and 54 μM, respectively) with good antioxidant activity. Molecular docking studies explored the detailed interaction pattern with active, peripheral, and mid-gorge sites of AChE. These compounds, exhibiting such multiple pharmacological activities, can be further taken a lead for the development of potent drugs for the treatment of Alzheimer’s disease.
- Singh, Manjinder,Kaur, Maninder,Vyas, Bhawna,Silakari, Om
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p. 520 - 530
(2017/10/09)
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- Rational design for multicolor flavone-based fluorophores with aggregation-induced emission enhancement characteristics and applications in mitochondria-imaging
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Fluorophores with aggregation-induced emission enhancement (AIEE) properties have attracted more attention in recent years. In order to realise more valuable applications, the different kinds of AIEE molecules are in serious need of further development. Therefore, a novel flavone-based AIEE system derived from restriction of intramolecular rotation (RIR) was designed and synthesized in this work. The results revealed that six of the compounds showed typical AIEE characteristics, with fluorescence emissions from purple, blue, cyan to green, tunable by changing substituent groups. This flavone-based AIEE system has never been reported before. The AIEE characteristics were investigated by optical spectroscopy, fluorescence photographs, scanning electron microscopy (SEM), fluorescence quantum yields (φF) and fluorescence lifetime in the CH3OH/H2O mixed solution. Moreover, benefiting from the simple structures and small molecular weight, they could permeate cells faster than current high-molecular-weight AIEE molecules. Furthermore, to examine possible biomedical applications, fluorescence imaging in living A549 lung cells and cell viabilities were examined, and the results displayed that these fluorophores showed good cellular uptake and low cytotoxicity within the experimental concentration range. In addition, these AIEE compounds possessed excellent specificity for mitochondrial targeting and mitochondrial morphological change tracking, besides, they displayed superior photostability, which indicated they are potential candidates for mitochondrial imaging.
- Liu, Liyan,Lei, Yaohui,Zhang, Jianhui,Li, Na,Zhang, Fan,Wang, Huaqiao,He, Feng
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- Design, synthesis of novel azolyl flavonoids and their protein tyrosine Phosphatase-1B inhibitory activities
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A series of azolyl flavonoids were synthesized and characterized by NMR, IR, MS and HRMS spectra. All the newly prepared compounds were screened for their potential protein tyrosine phosphatase inhibitory activities. Bioactive assay manifested that most of the azolyl flavonoids exhibited good protein phosphatase 1B (PTP1B) inhibitory activities. Especially, triazolyl flavonoid 6a displayed the best inhibitory activity (IC50 = 1.6 μM) with 9.9-fold selectivity for PTP1B over the closely related T-cell protein tyrosine phosphatase (TCPTP). Cell viability assays indicated 6a has lower cytotoxicity. Molecular modeling and dynamics studies revealed the reason of selectivity for PTP1B over TCPTP. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity.
- Zhang, Ling,Ge, Yu,Song, Hao Ming,Wang, Qing Ming,Zhou, Cheng-He
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p. 195 - 203
(2018/06/26)
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- A transition-metal-free fast track to flavones and 3-arylcoumarins
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A highly regioselective and transition-metal free one-pot arylation of chromenones with arylboronic acids has been achieved employing K2S2O8. The procedure consists of a sequence of some reactions including an arylation/decarboxylation cascade and proceeds well in aqueous media to afford biologically interesting flavones and 3-arylcoumarins. This method exhibited excellent selectivity and functional group tolerance under mild conditions. The reaction also showed perfect efficacy for the preparation of styryl coumarins.
- Golshani, Mostafa,Khoobi, Mehdi,Jalalimanesh, Nafiseh,Jafarpour, Farnaz,Ariafard, Alireza
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supporting information
p. 10676 - 10679
(2017/10/06)
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- Biological activity evaluation and molecular docking study of chromone derivatives as cyclooxygenase-2 inhibitors
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A series of chromone derivatives have been evaluated as potential cyclooxygenase-2 (COX-2) inhibitors. The four most potent compounds, 48, 41, 39, and 35 displayed IC50 values of 3.30, 6.86, 7.36 and 7.46 μM, respectively. Compounds 35 and 38 showed higher selectivity for COX-2 (selectivity index, SI = 7.48 and 5.46, respectively) than celecoxib (SI = 4.17 in the same test) whereas compound 39 showed comparable selectivity (SI = 4.19) to celecoxib. The molecular volumes of compounds 35 (312.84 ?3) and 38 (314.18 ?3) were similar to celecoxib (299.28 ?3) but larger than ibuprofen (211.83 ?3). Docking results were in good agreement with the experimental biological data in terms of evaluation of binding energy and binding mode. Compounds 35, 38, and 39 had higher binding affinity against COX-2 (binding energy between ?9.77 and ?11.42 kcal/mole) than COX-1 (binding energy between ?6.28 and ?7.88 kcal/mole). These three chromone compounds also displayed active conformation in the same orientation as that of celecoxib. Thus, compounds in this series has the potential to be a new class of selective COX-2 inhibitor.
- Maicheen, Chirattikan,Phosrithong, Narumol,Ungwitayatorn, Jiraporn
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p. 662 - 671
(2017/02/15)
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- Synthesis and antiproliferative activity of some dihydro-1 H-furo[2,3-c]pyrazole-Flavone hybrids
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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.
- Tangeti, Venkata Swamy,Vasundhara,Satyanarayana,Pavan Kumar, Kaja Srinivas
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p. 1525 - 1532
(2017/05/29)
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- Facile synthesis of acacetin and its derivatives
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Acacetin, a O-methylated bioflavonoid isolated from the traditional Chinese medicine Xuelianhua (Saussurea tridactyla), is a promising orally effective atrium-selective antiarrhythmic agent for the treatment of atrial fibrillation (AF). Here we describe an efficient two-component method for the synthesis of acacetin and its derivatives.
- Zhao, Yuan,Cai, Li,Sui, Qiang,Lin, Feng,Jiang, Wen,Chen, Jianli,Lu, Weigeng,Gao, Qi
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supporting information
p. 3577 - 3580
(2016/07/21)
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- Five-membered heterocycle (or amide)-flavonoid compound-matrine ternary conjugate and application thereof
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The invention discloses a five-membered heterocycle (or amide)-flavonoid compound-matrine ternary conjugate and application thereof. The five-membered heterocycle (or amide)-flavonoid compound-matrine ternary conjugate has a structure as shown in the specification, has an effective antibacterial activity, and has a potential application value in the aspect of antibacterial drug development. The five-membered heterocycle (or amide)-flavonoid compound-matrine ternary conjugate has a remarkable effect on the antibacterial aspect, and can be applied to prevention and treatment of MRSA, P.aeru, E.coli, Ab and other clinical common pathogens.
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Paragraph 0039; 0040
(2016/10/08)
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- Method for synthesizing flavonoids compound in one step by virtue of catalysis of 1,3-dialkylimidazolium oxometallate
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The invention discloses a method for synthesizing a flavonoids compound in one step by virtue of catalysis of 1,3-dialkylimidazolium oxometallate. The method is characterized by comprising the following steps: sequentially adding raw material benzaldehyde or benzaldehyde derivatives, raw material 2-hydroxyacetophenone or 2-hydroxyacetophenone derivatives, an ion liquid catalyst and an organic solvent into a reactor, stirring, heating to 50 to 90 DEG C, reacting for 2 to 7 hours at a constant temperature by taking oxygen or air as an oxidant, cooling, distilling under reduced pressure, carrying out the column chromatography, and re-crystallizing and separating to obtain the target product flavonoids compound. The method has the characteristics that the ion liquid is used as the catalyst, the yield of the flavonoids compound synthesized in one step reaches 85 percent or more, therefore, compared with the traditional synthetic method, the reaction flow is shortened, and the synthetic efficiency of the flavonoids compound is remarkably improved. The method has advantages of high product yield, low production cost, simple operation procedures, moderate reaction conditions and the like and is proved to be a novel method for high-efficiently synthesizing the flavonoids compound.
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Paragraph 0111; 0112; 0113; 0114; 0115
(2016/10/08)
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- Design, synthesis and evaluation of novel 7-aminoalkyl-substituted flavonoid derivatives with improved cholinesterase inhibitory activities
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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.
- Luo, Wen,Chen, Ying,Wang, Ting,Hong, Chen,Chang, Li-Ping,Chang, Cong-Cong,Yang, Ya-Cheng,Xie, Song-Qiang,Wang, Chao-Jie
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p. 672 - 680
(2016/02/09)
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- Synthesis of novel substituted pyrano annulated flavones
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A simple and efficient one pot method has been developed for the synthesis of some new functionalized pyrano fused flavone derivatives, alkyl 4,8-dioxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-10-carboxylates and dialkyl 4-oxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-8,9-dicarboxylates, from 7-hydroxy flavones and 7-hydroxy 8-formyl flavones using dialkylacetalynedicarboxylates in the presence of triphenyl phosphine. The structures of all synthesized compounds were elucidated by FT-IR, 1H and 13C NMR and Mass spectral analysis.
- Jayaprakash Rao,Thirupathi,Prasad Rao, Ch.,Hemasri
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p. 1126 - 1131
(2016/07/06)
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- Synthesis of Diverse Oxa-Carbocycle-Annulated Flavones Using the Combined Claisen Rearrangement and Ring-Closing Metathesis
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A simple and efficient route for the synthesis of oxepine-, oxocine-, oxepinone-, and dioxocine-angularly annulated flavone skeletons has been developed. The combined Claisen rearrangement and the ring-closing metathesis are used as key steps for the construction of C7/C8–C6–C6tricyclic core structures.
- Gogula, Thirupathi,Yerrabelly, Jayaprakash Rao
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p. 547 - 557
(2016/07/22)
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- Aldose reductase inhibitors for diabetic complications: Receptor induced atom-based 3D-QSAR analysis, synthesis and biological evaluation
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Herein, atom-based 3D-QSAR analysis was performed using receptor-guided alignment of 46 flavonoid inhibitors of aldose reductase (ALR2) enzyme. 3D-QSAR models were generated in PHASE programme, and the best model corresponding to PLS factor four (QSAR4), was selected based on different statistical parameters (i.e., Rtrain2, 0.96; Qtest2 0.81; SD, 0.26). The contour plots of different structural properties generated from the selected model were utilized for the designing of five new congener molecules. These designed molecules were duly synthesized, and evaluated for their in vitro ALR2 inhibitory activity that resulted in the micromolar (IC50 22 μM) activity of all molecules. Thus, the newly designed molecules having ALR inhibitory potential could be employed for the management of diabetic complications.
- Vyas, Bhawna,Singh, Manjinder,Kaur, Maninder,Bahia, Malkeet Singh,Jaggi, Amteshwar Singh,Silakari, Om,Singh, Baldev
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- Synthesis and anti-inflammatory in vitro, in silico, and in vivo studies of flavone analogues
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Chrysin and 7-hydroxy flavone were prepared by Baker-Venkatraman rearrangement followed by esterification at 7th position and replacement of ester with acetamide linking to different heterocyclic moieties synthesized 13a-g and 14a-g series of flavones analogues. These were screened against COX-2 and COX-1 enzymes for inhibition by in vitro assay and COX-2 for in silico docking studies. The compound 14a was found to be most active with IC50 of 3.11 μM concentration, with highest binding energy of -12.4 kcal/mole and 77.2 and 80.5 % inhibition at 3 and 5 h post-carrageenan induced in paw oedema.
- Khanapur, Manjulatha,Pinna, Nishal K.,Badiger, Jaishree
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p. 2656 - 2669
(2015/02/05)
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- Single and double intramolecular proton transfers in the electronically excited state of flavone derivatives
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In an attempt to create a flavone derivative able to take part in Excited State Intramolecular Double Proton Transfer (ESIDPT), we synthesized two carbonyl derivatives of 3,7-dihydroxyflavone, both containing two different proton-transfer sites as well as related carbonyl derivatives of 3-hydroxyflavone and 7-hydroxyflavone. All the examined hydroxyflavones were found to participate in the Excited State Intramolecular Proton Transfer (ESIPT). ESIPT which involves 3-hydroxyl and 4-carbonyl groups was found to have a higher barrier compared to ESIPT involving 7-hydroxyl and 6/8-carbonyl fragments. According to the data presented, 3,7-dihydroxy-2-phenyl-6-(3-phenylpropanoyl)-4H-chromen-4-one undergoes a two-stage ESIDPT with formation of an intermediate tautomer. This kind of ESIDPT leads to a tautomeric form with an abnormally low rate of radiative deactivation of the excited state, which conditions low fluorescence quantum yield. The behavior of 3,7-dihydroxy-4-oxo-2-phenyl-4H-chromene-8-carbaldehyde in the electronically excited state is similar to 3-hydroxyflavone derivatives, thus we conclude the occurrence of a single ESIPT in this compound.
- Serdiuk,Roshal
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p. 102191 - 102203
(2015/12/11)
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- Steroid Sulfatase Inhibitors Based on Phosphate and Thiophosphate Flavone Analogs
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Preclinical Research A series of phosphate and thiophosphate flavone derivatives were synthesized and biologically evaluated in vitro for inhibition of steroid sulfatase (STS) activity. The described synthesis includes the straightforward preparation of 7-hydroxy-2-phenyl-4H-chromen-4-one 3a, 2-(4-fluorophenyl)-7-hydroxy-4H-chromen-4-one 3b, 7-hydroxy-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one 3c, 7-hydroxy-2-(p-tolyl)-4H-chromen-4-one 3d modified with different phosphate or thiophosphate moieties. The inhibitory properties of the synthesized compounds were tested against human placenta STS. Some of the novel STS inhibitors had good activities against STS. In particular, the bis-(4-oxo-2-(p-tolyl)-4H-chromen-7-yl) hydrogenthiophosphate, 6i had the most potent inhibitory effect with an IC50 value of 3.25 μM as compared to an IC50 value of 8.50 μM for the 2-(4-trifluoromethylphenyl)-chromen-4-one-7-O-sulfamate used as a reference. Drug Dev Res 76: 450-462, 2015.
- Kozak, Witold,Dako, Mateusz,Maslyk, Maciej,Kubiski, Konrad,Rachon, Janusz,Demkowicz, Sebastian
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p. 450 - 462
(2016/01/28)
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- Metal-free catalytic cascade to chromones: Direct coupling of salicylaldehydes and activated alkynes triggered by aryloxyl radicals
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The first intermolecular addition reaction of aryloxyl radicals to CC bonds was disclosed, which can afford biologically important chromone scaffolds via a PhNMe3I-catalyzed direct coupling of readily available salicylaldehydes and activated internal alkynes in only one step, and can tolerate a range of catalytically reactive functional groups.
- Wang, Ping,Li, Zhongfeng,Cao, Shengli,Rao, Honghua
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p. 106350 - 106354
(2016/01/09)
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- A new synthesis for acacetin, chrysoeriol, diosmetin, tricin and other hydroxylated flavones by modified Baker-Venkataraman transformation
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Baker-Venkataraman (BV) rearrangement is the method of choice for the synthesis of flavones. The major limitation of BV is that it requires extensive protections and deprotections of hydroxyl groups which make the process lengthy and cumbersome. In the present study, a three step efficient method has been developed using simple protecting groups and easily available starting materials. New syntheses for acacetin, chrysoeriol, diosmetin, tricin and other hydroxylated flavones are described.
- Pandurangan
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p. 225 - 229
(2014/05/20)
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- Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease
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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.
- Li, Su-Yi,Wang, Xiao-Bing,Xie, Sai-Sai,Jiang, Neng,Wang, Kelvin D.G.,Yao, He-Quan,Sun, Hong-Bin,Kong, Ling-Yi
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p. 632 - 646
(2013/10/22)
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- Cyclization of 2'-hydroxychalcones to flavones using ammonium iodide as an iodine source - An eco-friendly approach
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Ammonium iodide on exposure to air decomposes to ammonia and iodine. The in situ generated iodine was used for the cyclization of 2'-hydroxychalcones to the corresponding flavones under solvent-free conditions in good to excellent yields. This method could serve as an attractive alternative to the existing methods for synthesis of flavones and the use of toxic molecular iodine is avoided. Copyright
- Kulkarni, Pramod S.,Kondhare, Dasharath D.,Varala, Ravi,Zubaidha, Pudukulathan K.
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p. 909 - 916
(2013/08/23)
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- Glucosylation of hydroxyflavones by glucosyltransferases from Phytolacca americana
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Cell suspension cultures of Phytolacca americana can glucosylate 6- and 7-hydroxyflavone, but not 5-hydroxyflavone. In order to identify the enzymes responsible for these transformations, glucosyltransferases (GTs) from P. americana were overexpressed in Escherichia coli and purified. The purified PaGT3 enzyme could glucosylate 6- and 7-hydroxyflavone when incubated with UDP-glucose, a glucosyl donor molecule, but PaGT2 could conjugate a glucose moiety only to 6-hydroxyflavone. E. coli cells expressing PaGT2 and 3 could also be utilized for the glucosylation of hydroxyflavones. The glucoside products which had accumulated in the medium of overnight E. coli cell cultures were isolated using hydrophobic resins. This methodology might be suitable for the glucosylation of aglycones with important health-related properties.
- Iwakiri, Tomoya,Mase, Shogo,Murakami, Tomonori,Matsumoto, Masahiro,Hamada, Hiroki,Nakayama, Toru,Ozaki, Shin-Ichi
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- COMPOUNDS THAT EXPAND HEMATOPOIETIC STEM CELLS
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The present invention relates to compounds and compositions for expanding the number of CD34+ cells for transplantation. The invention further relates to a cell population comprising expanded hematopoietic stem cells (HSCs) and its use in autologous or allogeneic transplantation for the treatment of patients with inherited immunodeficient and autoimmune diseases and diverse hematopoietic disorders to reconstitute the hematopoietic cell lineages and immune system defense.
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Page/Page column 33; 35
(2012/08/08)
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- Palladium-catalyzed dehydrogenation/oxidative cross-coupling sequence of β-heteroatom-substituted ketones
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Concise and selective: The title one-pot sequence allows formation of the enone functionality and subsequent cross-coupling. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible β-heteroatom-substitut
- Moon, Youngtaek,Kwon, Daeil,Hong, Sungwoo
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supporting information
p. 11333 - 11336,4
(2012/12/12)
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- Design, synthesis and biological evaluation of new arylpiperazine derivatives bearing a flavone moiety as α1-adrenoceptor antagonists
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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).
- Jin, Jing,Wang, Xiao-Bing,Kong, Ling-Yi
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scheme or table
p. 909 - 911
(2011/03/20)
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- Synthesis, in vitro evaluation, and docking studies of novel chromone derivatives as HIV-1 protease inhibitor
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Novel chromone derivatives with a benzopyran-4-one scaffold have been prepared by the one-pot cyclization reaction. The in vitro inhibitory activity of these new compounds towards HIV-1 protease have been evaluated using stop time HPLC method as the preliminary screening. The most potent compound, 7,8-dihydroxy-2-(3′-trifluoromethyl phenyl)-3-(3″- trifluoromethylbenzoyl)chromone (32), showed IC50 = 0.34 μM. The molecular docking study supported results from experimental activity testing and also provided structure-activity relationship of this series.
- Ungwitayatorn, Jiraporn,Wiwat, Chanpen,Samee, Weerasak,Nunthanavanit, Patcharawee,Phosrithong, Narumol
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p. 152 - 161
(2011/10/03)
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- An efficient one-pot synthesis of flavones
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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.
- Chee, Chin Fei,Buckle, Michael J.C.,Rahman, Noorsaadah Abd.
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supporting information; experimental part
p. 3120 - 3123
(2011/06/26)
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- Facile synthesis of 9-acetyl/formyl/cyano-substituted pyrano[2,3-f]flavones and chromones using the baylis-hillman reaction
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Condensation of 8-formyl-7-hydroxyflavones (2a-f) and 8-formyl-7-hydroxy-2- (2'-furyl)-3-methylchromone (2g) with methyl vinyl ketone (3), acrolein (4), and acrylonitrile (5) in the presence of diazabicyclo[2.2.2]octane (DABCO) under an N2 atmosphere at room temperature using Baylis-Hillman reaction conditions afforded 9-acetyl/formyl/cyano-substituted pyrano2,3-f]flavones (6a-f, 7a-f, 8a-f) and chromones (6g, 7g, 8g).
- Reddy, S. Satyanarayana,Krupadanam, G. L. David
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experimental part
p. 1292 - 1304
(2010/06/20)
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- Synthesis of flavonoid 7-O-β-D-glycosides by phase transfer catalysis
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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.
- Wu, Zheng,Jiang, Ling,Chen, He,Wang, Qiu-An
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experimental part
p. 195 - 197
(2009/11/30)
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- Mechanically activated solid-state synthesis of flavones by high-speed ball milling
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An efficient, mechanically activated solid-state synthesis of flavones from 1-(2-hydroxyphenyl)-3-aryl-1,3-propanediones using high-speed ball milling is described. This method has notable advantages in terms of good yield, short reaction time, and neat conditions.
- Zhu, Xingyi,Li, Zhenhua,Shu, Qiangfeng,Zhou, Chenfeng,Su, Weike
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experimental part
p. 4199 - 4211
(2010/01/16)
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- Facile synthesis of 7-methoxy-2-aryl-3-phenyl/or-H-8-[2-(4,6-dimethyl-3,5- dicarbethoxy-pyridyl)]-4H-1-benzopyran-4-ones
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Condensation of 8-formyl-7-methoxy-2-phenyl-4H-1-benzopyran-4-ones (5a-f) with ethyl-3-aminocrotonate (6) in glacial acetic acid under Hantzsch conditions afforded 7-methoxy-2-aryl-3-phenyl/or-H-8-[2-(4,6-dimethyl-3,5-dicarbethoxy- pyridyl)]-4H-1-benzopyran-4-ones (7a-f) in good yields. Copyright Taylor & Francis Group, LLC.
- Soni, Anil Kumar,Krupadanam, G. L. David,Srimannarayana
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p. 795 - 804
(2007/10/03)
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- Synthesis of oxygen heterocycles
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A generalised scheme for the synthesis of flavones, flavonones and chromones involving 3-acyl-γ-pyrone intermediates has been developed. Convenient synthesis of other oxygen heterocycles using similar procedure have been outlined.
- Ganguly,Mahata,Biswas
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p. 1347 - 1349
(2007/10/03)
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- Synthesis and properties of 3-acyl-γ-pyrones, a novel class of flavones and chromones
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Using modified Baker-Venkataraman reaction a novel class of 3-acyl flavones and chromones have been synthesised. Reaction mechanism for their formation have been elucidated. The properties of 3-acyl flavonoids indicate them to be precursors for the synthesis of flavones.
- Ganguly,Kaur,Mahata,Biswas,Pramanik,Chan
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p. 4119 - 4121
(2007/10/03)
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- FeCl3 catalyzed dehydrative cyclisation of 1, 3 - (diaryl diketones) to flavones
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FeCl3 in catalytic amount effects smooth conversion of substituted 1- (2-hydroxy phenyl) - 3 - phenyl - 1, 3 - propanediones to the corresponding flavones in high yields.
- Zubaidha,Hashmi,Bhosale
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- Microwave-assisted synthesis of functionalized flavones and chromones
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A facile microwave synthesis of functionalized flavones and chromones via the cyclization of 1-(2-hydroxyaryl)-3-aryl-1,3-propanedione is described.
- Kabalka, George W.,Mereddy, Arjun R.
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p. 6315 - 6317
(2007/10/03)
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- Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives
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A series of chrysin derivatives were prepared and evaluated for their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin production. Chrysin derivatives were prepared from 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone in 2 to 4 steps, respectively. Methxoylated chrysin derivatives were converted to the corresponding hydroxylated chrysin derivatives by the reaction with BBr 3 in good yields. The inhibitory activity of the chrysin derivatives against prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells was measured. We found that chrysin derivatives with 3′,4′- dichloro substituents (5e, 6e and 7e) exhibited good inhibitory activity of prostaglandin production.
- Dao, Tran Thanh,Chi, Yeon Sook,Kim, Jeongsoo,Kim, Hyun Pyo,Kim, Sanghee,Park, Haeil
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p. 1165 - 1167
(2007/10/03)
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- Cleavage of methyl ethers of flavones by chloroaluminate ionic liquid
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A new o-demethylation method of a series of mono-, di-, trimethoxy-flavones using a chloroaluminate ionic liquid - [BMIM] [Al2Cl7] in dichloromethane is described. The desired products were obtained in moderate to good yields.
- Liu, Tao,Hu, Yongzhou
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p. 3209 - 3218
(2007/10/03)
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