- Design and synthesis of chromone-nitrogen mustard derivatives and evaluation of anti-breast cancer activity
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Chromone has emerged as one of the most important synthetic scaffolds for antitumor activity, which promotes the development of candidate drugs with better activity. In this study, a series of nitrogen mustard derivatives of chromone were designed and syn
- Sun, Jianan,Mu, Jiahui,Wang, Shenglin,Jia, Cai,Li, Dahong,Hua, Huiming,Cao, Hao
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p. 431 - 444
(2022/01/04)
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- Synthesis and biological evaluation of 3-styrylchromone derivatives as selective monoamine oxidase B inhibitors
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A series of 3-styrylchromone derivatives was synthesized and evaluated for monoamine oxidase (MAO) A and B inhibitory activities. Most of all derivatives inhibited MAO-B selectively, except compound 21. Compound 19, which had a methoxy group at R2 on the chromone ring and chlorine at R4 on phenyl ring, potently inhibited MAO-B, with an IC50 value of 2.2 nM. Compound 1 showed the highest MAO-B selectivity, with a selectivity index of >3700. Further analysis of these compounds indicated that compounds 1 and 19 were reversible and mixed-type MAO-B inhibitors, suggesting that their mode of action may be through tight-binding inhibition to MAO-B. Quantitative structure–activity relationship (QSAR) analyses of the 3-styrylchromone derivatives were conducted using their pIC50 values, through Molecular Operating Environment (MOE) and Dragon. There were 1796 descriptors of MAO-B inhibitory activity, which showed significant correlations (P 50 value index exhibited a determination coefficients (R2) of 0.972 and a Leave-One-Out cross-validated determination coefficients (Q2) of 0.914. These data suggest that the 3-styrylchromone derivatives assessed herein may be suitable for the design and development of novel MAO inhibitors.
- Takao, Koichi,Takemura, Yuri,Nagai, Junko,Kamauchi, Hitoshi,Hoshi, Kaori,Mabashi, Ryo,Uesawa, Yoshihiro,Sugita, Yoshiaki
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- Discovery of Novel Chromone Derivatives Containing a Sulfonamide Moiety as Anti-ToCV Agents through the Tomato Chlorosis Virus Coat Protein-Oriented Screening Method
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A number of novel chromone derivatives containing sulfonamide moieties were designed and synthesized, and the activity of compounds against tomato chlorosis virus (ToCV) was assessed using the ToCVCP-oriented screening method. Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were established based on the dissociation constant (Kd) values of the target compounds, and compound 35 was designed and synthesized with the aid of CoMFA and CoMSIA models. The study of affinity interaction indicated that compound 35 exhibited excellent affinity with ToCVCP with a Kd value of 0.11 μM, which was better than that of the positive control agents xiangcaoliusuobingmi (0.44 μM) and ningnanmycin (0.79 μM). In addition, the in vivo inhibitory effect of compound 35 on the ToCVCP gene was evaluated by the quantitative real-time polymerase chain reaction. ToCVCP gene expression levels of the compound 35 treatment group were reduced by 67.2%, which was better than that of the positive control agent ningnanmycin (59.5%). Therefore, compound 35 can be used as a potential anti-ToCV drug in the future.
- Jiang, Donghao,Chen, Jixiang,Zan, Ningning,Li, Chunyi,Hu, Deyu,Song, Baoan
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p. 12126 - 12134
(2021/10/26)
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- Novel p-functionalized chromen-4-on-3-yl chalcones bearing astonishing boronic acid moiety as MDM2 inhibitor: Synthesis, cytotoxic evaluation and simulation studies
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Background: Novel 4-[3-(6/7/8-Substituted 4-Oxo-4H-chromen-3-yl)acryloyl]phenyl-boronic acid derivatives (5a-h) as well as other 6/7/8-substituted-3-(3-oxo-3-(4-substituted-phenyl)prop-1-enyl)-4H-chromen-4-one derivatives (3a-u) have been designed as p53-MDM2 pathway inhibitors and reported to possess significant cytotoxic properties against several cancer cell lines. Objectives: The current project aims to frame the structure-anticancer activity relationship of chromen-4-on-3-yl chalcones (3a-u/5a-h). In addition, docking studies were performed on these chromeno-chalcones in order to have an insight into their interaction possibilities with MDM2 pro-tein. Methods: Twenty-nine chromen-4-on-3-yl chalcone derivatives (3a-u/5a-h) were prepared by utilizing silica supported-HClO4 (green route with magnificent yield) and tested against four cancer cell lines (HCT116, MCF-7, THP-1, NCIH322). Results: Among the series 3a-u, compound 3b exhibited the highest anticancer activity (with IC50 values ranging from 8.6 to 28.4 μM) overall against tested cancer cell lines. Interestingly, para-Boronic acid derivative (5b) showed selective inhibition against colon cancer cell line, HCT-116 with an IC50 value of 2.35 μM. Besides the emblematic hydrophobic interactions of MDM2 inhibi-tors, derivative 5b was found to exhibit extra hydrogen bonding with GLN59 and GLN72 residues of MDM2 in molecular dynamics (MD) simulation. All the compounds were virtually nontoxic against normal fibroblast cells. Conclusion: Novel compounds were obtained with good anticancer activity especially 6-Chlorochromen-4-one substituted boronic acid derivative 5b. The molecular docking study proposed good activity as a MDM-2 inhibitor suggesting hydrophobic as well as hydrogen bonding interactions with MDM2.
- Bhatia, Richa Kaur,Coutinho, Evans C.,Garg, Ruchika,Kancherla, Satyavathi,Kaur, Maninder,Madan, Jitender,Pissurlenkar, Raghuvir R. S.,Singh, Lakhwinder,Yadav, Manmohan
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p. 212 - 228
(2020/03/10)
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- Synthesis and biological evaluation of chromone-3-carboxamides
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The aim of our study was to synthesize novel chromone-3-carboxamides and to conduct biological evaluations in search for lead compounds for the treatment of a range of debilitating disease states. Corresponding 2-hydroxyacetophenones were subjected to Vilsmeier-Haack formylation to give chromone-3-carbaldehydes, which were subsequently oxidised to give chromone-3-carboxylic acids. Treatment of the carboxylic acids with thionyl chloride resulted in the in situ formation of the corresponding acid chlorides, which were reacted with various amines in the presence of triethylamine to give the corresponding novel chromone-3-carboxamides in good yields. Selected chromone derivatives were then evaluated for their anti-inflammatory, anti-tryponosomal and cytotoxic properties.
- Gordon, Allen T.,Ramaite, Isaiah D.I.,Mnyakeni-Moleele, Simon S.
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p. 148 - 160
(2021/01/20)
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- Antiproliferative chromone derivatives induce K562 cell death through endogenous and exogenous pathways
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A series of furoxan derivatives of chromone were prepared. The antiproliferative activities were tested against five cancer cell lines HepG2, MCF-7, HCT-116, B16, and K562, and two normal human cell lines L-02 and PBMCs. Among them, compound 15a exhibited the most potent antiproliferative activity. It was also found 15a produced more than 8 μM of NO at the peak time of 45 min by Griess assay. Generally, antiproliferative activity is positively related to NO release to some extent. Further in-depth studies on apoptosis-related mechanisms showed that 15a caused S-phase cell cycle arrest in a concentration-dependent manner and induced apoptosis significantly through mitochondria-related pathways. Human apoptosis protein array assay also demonstrated 15a increased the expression levels of pro-apoptotic Bax, Bad, HtrA2 and Trail R2/DR5. The expression of catalase and cell cycle blocker claspin were similarly up-regulated. In balance, 15a induced K562 cells death through both endogenous and exogenous pathways.
- Cao, Hao,Hua, Huiming,Huang, Xiaofang,Jiao, Runwei,Li, Dahong,Li, Haonan,Li, Zhanlin,Liu, Weiwei,Xu, Fanxing,Zang, Linghe
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p. 759 - 772
(2020/04/01)
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- Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease
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A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC50 = 5.24 μM; AChE: IC50 = 0.37 μM) and hMAO-B selectivity (IC50 = 0.272 μM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.
- Huang, Ming,Jiang, Neng,Kong, Ling-Yi,Lan, Jin-Shuai,Wang, Xiao-Bing,Yin, Fu-Cheng
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p. 225 - 233
(2020/04/22)
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- Organocatalytic [10+4] cycloadditions for the synthesis of functionalised benzo[a]azulenes
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A direct and mild strategy for the synthesis of benzo[a]azulenes based on an organocatalytic [10+4] cycloaddition reaction is described. The strategy enables a diversity-oriented approach for the synthesis of various poly-functionalised azulenes from easily accessible starting materials.
- Giardinetti, Maxime,Jessen, Nicolaj Inunnguaq,Christensen, Mette Louise,J?rgensen, Karl Anker
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supporting information
p. 202 - 205
(2019/01/04)
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- One pot and metal-free approach to 3-(2-Hydroxybenzoyl)-1-aza-anthraquinones
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Herein, a direct strategy to synthesize 3-(2-hydroxybenzoyl)-1-aza-anthraquinones with excellent efficiency,mild conditions, and benign functional group compatibilitywas reported. Avariety of 3-formylchromone compounds were employed as compatible substrates and this protocol gave the 3-(2-hydroxybenzoyl)-1-aza-anthraquinone derivatives in good to excellent yields without inert gas and expensive transition metal catalysts. Some compounds displayed good anti-proliferative activities.
- Yuan, Jiaqi,He, Qian,Song, Shanshan,Zhang, Xiaofei,Miao, Zehong,Yang, Chunhao
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supporting information
(2019/08/30)
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- Coumarin versus Chromone Monoamine Oxidase B Inhibitors: Quo Vadis?
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Because of the lack of significant disease-modifying drugs for neurodegenerative disorders, a pressing need for new chemical entities endowed with IMAO-B still exists. Within this framework, and for the first time, a study was performed to compare coumari
- Fonseca, André,Reis, Joana,Silva, Tiago,Matos, Maria Jo?o,Bagetta, Donatella,Ortuso, Francesco,Alcaro, Stefano,Uriarte, Eugenio,Borges, Fernanda
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supporting information
p. 7206 - 7212
(2017/09/07)
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- Synthesis and biological evaluation of N-Aryl-N′-(5-(2-hydroxybenzoyl) pyrimidin-2-yl)guanidines as toll-like receptor 4 antagonists
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Background: Toll-like receptor 4 (TLR4) has been associated with several inflammatory diseases, such as sepsis, atherosclerosis and chronic pain. Objective: The aim of the present study was to develop an efficient and straightforward synthetic approach for the preparation of small-molecule antagonists Naryl-N′-(5-(2-hydroxybenzoyl)pyrimidin-2-yl)guanidines in order to evaluate these for TLR4 antagonist activity and to obtain useful information about their structure-activity relationships. Methods: The present work have designed and optimized a three-step synthetic route for derivatives of a previously demonstrated antagonist of TLR4: 1-(4-fluorophenyl)-2-(5-(2-hydroxy-5-methoxybenzoyl)pyrimidin-2-yl)guanidine. The antagonist activities of eight novel synthesized compounds were evaluated on cells which selectively express TLR4. Results: Three guanidine derivatives showed promising antagonist activities, with IC50 values in the low micromolar range. Conclusion: Our findings represent an important starting point for further studies of small-molecule agents targeting Toll-like receptors.
- Sova, Matej,Ro?man, Kaja,?vajger, Urban,Ro?man, Primo?,Gobec, Stanislav
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p. 742 - 750
(2016/11/29)
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- Direct construction of xanthene and benzophenone derivatives via Br?nsted acid controlled Diels-Alder reaction of 3-vinylchromones and arynes
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A Br?nsted acid controlled Diels-Alder reaction of 3-vinylchromones with arynes has been developed. By employing different kinds and amounts of acid, 9-aryl-9H-xanthen-9-ols or ortho-hydroxybenzophenones could be controllably furnished in good yields in an atom- and step-economic manner.
- Huang, Xu-Jiao,Tao, Yuan,Li, Yue-Kun,Wu, Xin-Yan,Sha, Feng
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supporting information
p. 8565 - 8577
(2016/12/09)
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- Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: Synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression
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A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.
- Nazreen, Syed,Alam, Mohammad Sarwar,Hamid, Hinna,Yar, Mohammad Shahar,Dhulap, Abhijeet,Alam, Perwez,Pasha,Bano, Sameena,Alam, Mohammad Mahboob,Haider, Saqlain,Kharbanda, Chetna,Ali, Yakub,Pillai
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p. 3034 - 3042
(2014/06/24)
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- Synthesis and biological evaluation of 3-styrylchromone derivatives as free radical scavengers and α-glucosidase inhibitors
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A series of 3-styrylchromone derivatives (4-20) were synthesized and the structure-activity relationships for α-glucosidase inhibition and antioxidant activities were analyzed. Among the synthesized compounds, compounds 15 and 20, which contain a catechol moiety, showed both potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity (15: EC50 =17 μM; 20: EC50 =23 μM) and α-glucosidase inhibitory activity (15: IC50 =16 μM; 20: IC50 =10 μM). Our data suggest that 3-styrylchromone derivatives are novel α-glucosidase inhibitors that have the potential to counteract diet-induced hyperglycemia in diabetes.
- Takao, Koichi,Ishikawa, Ryo,Sugita, Yoshiaki
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p. 810 - 815
(2016/10/12)
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- Synthesis and characterization and anti-inflammatory and antibacterial evaluation of 3-arylidene-7-methoxychroman-4-ones
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3-Arylidene-7-methoxychroman-4-ones 3a-k have been prepared from 7-methoxy-chroman-4-one 1 and heterocyclic aldehydes 2 and have been evaluated for anti-inflammatory and antibacterial activities. All of them have registered moderate anti-inflammatory and antibacterial activities.
- Shankar,Gandhidasan,Venkataraman
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experimental part
p. 1202 - 1207
(2011/10/13)
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- Catalytic effects in baylis-hillman reactions of chromone-3-carbaldehydes with acrylonitrile and methyl acrylate
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The effects of various catalysts, the solvent system, and the temperature on the efficiency and chemoselectivity of reactions of a series of chromone-3-carbaldehydes with acrylonitrile and methyl acrylate are discussed.
- Molefe, Duduzile M.,Kaye, Perry T.
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scheme or table
p. 3586 - 3600
(2009/12/09)
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- Chromone studies. Part 17. Tricyclic scaffolds from reactions of chromone- 3-carbaldehydes and methyl vinyl ketone under Baylis-Hillman conditions
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Reaction of a series of chromone-3-carbaldehydes with methyl vinyl ketone under Baylis-Hillman conditions, sing 3-hydroxyquinuclidine in chloroform or DABCO in 1-methyl-2-pyrrolidinone, affords unprecedented tricylic hromone derivatives which, depending on the conditions, may be accompanied by the normal Baylis-Hillman roducts or their respective tricycl ic dimers.
- Molefe, Duduzile M.,Ganto, Mlungiseleli M.,Lobb, Kevin A.,Kaye, Perry T.
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scheme or table
p. 452 - 456
(2010/01/16)
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- Microwave-induced synthesis and regio- and stereoselective epoxidation of 3-styrylchromones
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The microwave-assisted solvent-free synthesis of (E)-3-styrylchromones from 3-formylchromones and phenylmalonic acid on sodium acetate support has been developed; the method affords the styryl derivatives in moderate to good yields and with complete diastereoselectivity. Protocols for the highly regioselective epoxidation of (E)- and (Z)-3-styrylchromones have been elaborated. Treatment of the alkenes with dimethyldioxirane led to the exclusive formation of 3-(3-aryloxiran-2-yl)chromones with complete diastereoselectivity, whereas treatment with hydrogen peroxide under alkaline conditions afforded the corresponding 2,3-epoxy-3-styrylchromanones as the only products. Epoxidation performed in the presence of chiral, nonracemic cinchona-alkaloid-based quaternary ammonium salts allowed the synthesis of enantiomerically enriched 2,3-epoxy-3-styrylchromanones, but with only moderate ee values. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Patonay, Tamas,Kiss-Szikszai, Attila,Silva, Vera M. L.,Silva, Artur M. S.,Pinto, Diana C. G. A.,Cavaleiro, Jose A. S.,Jeko, Jozsef
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body text
p. 1937 - 1946
(2009/04/04)
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- Improved selective reduction of 3-formylchromones using basic alumina and 2-propanol
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Treatment of formylchromones, dissolved in 2-propanol with basic alumina at 75°C, selectively reduces the formyl group with good yields without any activation process of the alumina.
- Araya-Maturana, Ramiro,Heredia-Moya, Jorge,Pessoa-Mahana, Hernan,Weiss-Lopez, Boris
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p. 3225 - 3231
(2007/10/03)
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- Structure-activity relationships of a novel class of endothelin-A receptor antagonists and discovery of potent and selective receptor antagonist, 2-(benzo[1,3]dioxol-5-yl)-6-isopropyloxy-4- (4-methoxyphenyl)-2H-chromene-3-carboxylic acid (S-1255). 1. Study on structure-activity relationships and basic structure crucial for ETA antagonism
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A novel series of endothelin-A (ETA) selective receptor antagonists having a 2H-chromene skeleton are described. A lead compound, 2-(benzo[1,3] dioxol-5-yl)-2H-chromene-3-carboxylic acid (3), was found by modifications of our own angiotensin II antagonist. A structure-activity relationship (SAR) study of 3 reveals that the structural requirements essential for potent and selective ETA receptor binding affinity are the m,p-methylenedioxyphenyl, carboxyl, and isopropoxy groups at the 2-, 3-,and 6-positions, respectively, on the (R)-2H-chromene skeleton. The substituent at the 4-position is also important for improving the activity, and various hydrophobic functional groups of 6-9 ? such as liner, branched, and cyclic aliphatic groups, unsubstituted and substituted aryl groups, and even halogen atoms were acceptable. These results suggest that (R)-2-(benzo[1,3]dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acid, formula 108, is the crucial basic structure to be recognized by the ETA receptor. The most potent compound is (R)-48 (S-1255), which binds to the ETA receptor with an IC50 value of 0.19 nM and is 630-fold selective for the ETA receptor than for the ETB receptor. This compound has 55% oral bioavailability in rats. On the basis of the SAR, the roles of each substituent in the receptor binding are discussed.
- Ishizuka, Natsuki,Matsumura, Ken-Ichi,Sakai, Katsunori,Fujimoto, Masafumi,Mihara, Shin-Ichi,Yamamori, Teru
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p. 2041 - 2055
(2007/10/03)
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- Synthesis of dihydroxanthone derivatives and evaluation of their inhibitory activity against acetylcholinesterase: Unique structural analogs of tacrine based on the BCD-ring of arisugacin
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A general approach to synthesis of dihydroxanthone derivatives is described here. In vitro evaluation of these dihydroxanthones demonstrated that some derivatives possess moderate anti-cholinesterase activities and better selectivities than tacrine for acetylcholinesterase over butyrylcholinesterase. Structural effects on anti-cholinesterase activities were also examined, and docking experiments were carried out to provide preliminary understandings of these experimental observations.
- Degen, Shane J.,Mueller, Kristen L.,Shen, Hong C.,Mulder, Jason A.,Golding, Geoffrey M.,Wei, Lin-li,Zificsak, Craig A.,Neeno-Eckwall, Amy,Hsung, Richard P.
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p. 973 - 978
(2007/10/03)
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- Chromonealdehyde compounds and process for the production thereof
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There are provided compounds of the general formula SPC1 Wherein R is a hydroxy, alkyl, acyloxy, halogen, nitro, substituted or unsubstituted amino, alkoxy, carboxy or a group derived from a carboxy group and m is 0, 1 or 2 except where m is 2, the two R groups are both hydroxy groups. The present invention is also concerned with a process for preparing the chromonealdehyde compounds. The chromonealdehyde compounds are characterized by antiallergic properties and are therefore useful as prophylactic and therapeutic agents for allergic asthma, allergic dermatitis and other allergic diseases and also are valuable as intermediates for the synthesis of other pharmaceutical compounds having the chromone nucleus.
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