- Synthesis and anti-tumor activity of novel aminomethylated derivatives of isoliquiritigenin
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A series of new aminomethylated derivatives of isoliquiritigenin was synthesized. The structures of the compounds were confirmed by IR, MS, NMR, 13C-NMR and elemental analyses. Cytotoxic activities of these derivatives towards the human prostatic cell line PC-3, human mammary cancer cell line MCF-7 and human oophoroma cell line HO-8910 in vitro were tested. The IC50 values showed cytotoxic activities of some of these new derivatives were relatively strong. Furthermore, tumor growth inhibition in vivo of aminomethylated derivatives of isoliquiritigenin 15 was superior to that of isoliquritigenin and reached inhibition rates of 71.68%. The detailed synthesis, spectroscopic data, biological and pharmacologicalactivities of the synthesized compounds were provided.
- Fu, Haoran,Zhang, Yuhang,Wang, Xiqing,Han, Yingzhi,Peng, Xiao,Efferth, Thomas,Fu, Yujie
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- Design, synthesis, and evaluation of 1, 4-benzodioxan-substituted chalcones as selective and reversible inhibitors of human monoamine oxidase B
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The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for the
- Kong, Zhuo,Sun, Demeng,Jiang, Yanmei,Hu, Yun
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Read Online
- Screening, synthesis, and evaluation of novel isoflavone derivatives as inhibitors of human Golgi β-galactosidase
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The genes GLB1 and GALC encode GLB1 isoform 1 and galactocerebrosidase, respectively, which exhibit β-galactosidase activity in human lysosomes. GLB1 isoform 1 has been reported to play roles in rare lysosomal storage diseases. Further, its β-galactosidase activity is the most widely used biomarker of senescent and aging cells; hence, it is called senescence-associated β-galactosidase. Galactocerebrosidase plays roles in Krabbe disease. We previously reported a novel β-galactosidase activity in the Golgi apparatus of human cells; however, the protein responsible for this activity could not be identified. Inhibitor-derived chemical probes can serve as powerful tools to identify the responsible protein. In this study, we first constructed a cell-based high-throughput screening (HTS) system for Golgi β-galactosidase inhibitors, and then screened inhibitors from two compound libraries using the HTS system, in vitro assay, and cytotoxicity assay. An isoflavone derivative was identified among the final Golgi β-galactosidase inhibitor compound hits. Molecular docking simulations were performed to redesign the isoflavone derivative into a more potent inhibitor, and six designed derivatives were then synthesized. One of the derivatives, ARM07, exhibited potent inhibitory activity against β-galactosidase, with an IC50 value of 14.8 μM and competitive inhibition with Ki value of 13.3 μM. Furthermore, the in vitro and cellular inhibitory activities of ARM07 exceeded those of deoxygalactonojirimycin. ARM07 may contribute to the development of affinity-based chemical probes to identify the protein responsible for the newly discovered Golgi β-galactosidase activity. The therapeutic relevance of ARM07 against lysosomal storage diseases and its effect on senescent cells should be evaluated further.
- Miura, Kazuki,Onodera, Chihiro,Takagi, Motonari,Koyama, Ryosuke,Hirano, Takako,Nishio, Toshiyuki,Hakamata, Wataru
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p. 753 - 761
(2020/09/18)
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- Isoflavone type compound as well as preparation method and application thereof
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The invention provides an isoflavone type compound and a preparation method thereof. A structural formula of the isoflavone type compound is shown as a formula and the formula is shown in the description, wherein R is a formula shown in the description, a
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Paragraph 0045; 0046; 0048
(2019/06/11)
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- Highly selective carbamate-based butyrylcholinesterase inhibitors derived from a naturally occurring pyranoisoflavone
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This current study described the design and synthesis of a series of derivatives based on a natural pyranoisaflavone, which was obtained from the seeds of Millettia pachycarpa and displayed attractive BChE inhibition and high selectivity in our previous study. The inhibitory potential of all derivatives against two cholinesterases was evaluated. Only a few compounds demonstrated AChE inhibitory activity at the tested concentrations, while 26 compounds showed significant inhibition on BChE (the IC50 values varied from 9.34 μM to 0.093 μM), most of them presented promising selectivity to ward BChE. Prediction of ADME properties for 7 most active compounds was performed. Among them, 9g (IC50 = 222 nM) and 9h (IC50 = 93 nM) were found to be the most potent BChE inhibitors with excellent selectivity over AChE (SI ratio = 1339 and 836, respectively). The kinetic analysis demonstrated both of them acted as mixed-type BChE inhibitors, while the molecular docking results indicated that they interacted with both residues in the catalytic active site. A cytotoxicity test on PC12 cells showed that both 9g and 9h had a therapeutic safety range similar to tacrine. Overall, the results indicate that 9h could be a good candidate of BChE inhibitors.
- Wu, Chuanhai,Tu, Yan-bei,Li, Ziyuan,Li, Yan-fang
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- Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents
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Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search
- Andrade, Jéssica T.,Santos, Felipe R. S.,Lima, William G.,Sousa, Carla D. F.,Oliveira, Lohanna S. F. M.,Ribeiro, Rosy I. M. A.,Gomes, Ana J. P. S.,Araújo, Marcelo G. F.,Villar, José A. F. P.,Ferreira, Jaqueline M. S.
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p. 702 - 712
(2018/04/26)
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- NOTCH INHIBITORS FOR USE IN THE TREATMENT OF T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
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Compounds of formula (I) in the capacity of compounds with anti-tumor activity for the treatment of T-cell acute lymphoblastic leukemia (T-ALL).
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Page/Page column 24-25
(2018/07/29)
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- Synthesis, characterization, and antioxidant activity of Zn2+ and Cu2+ coordinated polyhydroxychalcone complexes
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Four new metal complexes [Cu(ISO)2], [Cu(BUT)2] and [Zn(ISO)2], [Zn(BUT)2] of the polyhydroxychalcones (isoliquiritigenin and butein) are synthesized, structurally characterized and their antioxidant activity is investigated. The formation of the complexes [Cu(ISO)2] and [Zn(ISO)2] is followed by Job’s plot using NMR titration. The resulting compounds are characterized by mass spectrometry, IR spectroscopy, and elemental analysis. Studies on the radical scavenging activity are performed using DPPH as substrate. The results showed that the antioxidant activities of isoliquiritigenin and butein are enhanced after binding to copper or zinc. Graphical abstract: [Figure not available: see fulltext.]
- Sulpizio, Chiara,Müller, Simon T. R.,Zhang, Qi,Brecker, Lothar,Rompel, Annette
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p. 1871 - 1881
(2016/10/22)
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- Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin
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Abstract The synthesis and antimycobacterial activity of formononetin analogues is hereby reported. Formononetin and its analogue 11E showed 88% and 95% growth inhibition, respectively, against the H37Rv strain of Mycobacterium tuberculosis. Pharmacophore modeling studies indicated that the presence of a hydroxyl group in formononetin and its analogues, is crucial for maintaining activity.
- Mutai, Peggoty,Pavadai, Elumalai,Wiid, Ian,Ngwane, Andile,Baker, Bienyameen,Chibale, Kelly
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supporting information
p. 2510 - 2513
(2015/06/02)
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- Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
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A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 μM. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer.
- Wang, Guangcheng,Li, Chunyan,He, Lin,Lei, Kai,Wang, Fang,Pu, Yuzi,Yang, Zhuang,Cao, Dong,Ma, Liang,Chen, Jinying,Sang, Yun,Liang, Xiaolin,Xiang, Mingli,Peng, Aihua,Wei, Yuquan,Chen, Lijuan
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p. 2060 - 2079
(2014/04/17)
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- Synthesis, structure-activity relationships and biological evaluation of barbigerone analogues as anti-proliferative and anti-angiogenesis agents
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A series of barbigerone analogues (7a-7w, 13a-13x) were designed, synthesized and biologically evaluated for their anti-proliferative and anti-angiogenic activities. Among these compounds, compound 13a exhibited the most potent inhibitory effect on the proliferation of HUVECs, HepG2, A375, U251, B16, and HCT116 cells (IC50 = 3.80, 0.28, 1.58, 3.50, 1.09 and 0.68 μM, respectively). Compound 13a inhibited the angiogenesis in zebrafish embryo assay in a concentration-dependent manner. Furthermore, 13a also effectively inhibited the migration and capillary like tube formation of human umbilical vein endothelial cell in vitro. These results support the further investigation of this class of compounds as potential anti-proliferative and anti-angiogenesis agents.
- Wang, Guangcheng,Wang, Fang,Cao, Dong,Liu, Yibin,Zhang, Ronghong,Ye, Haoyu,Li, Xiuxia,He, Lin,Yang, Zhuang,Ma, Liang,Peng, Aihua,Xiang, Mingli,Wei, Yuquan,Chen, Lijuan
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supporting information
p. 3158 - 3163
(2014/06/24)
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- Synthesis and investigation of dihydroxychalcones as calpain and cathepsin inhibitors
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In order to identify potential calpain and cathepsin inhibitors we prepared 12 dihydroxychalcone analogues and tested their ability to inhibit μ-calpain, m-calpain, cathepsins B and L. In the calpain inhibition test, compound 10 exhibited the most active
- Baek, Kyung Hye,Karki, Radha,Lee, Eung-Seok,Na, Younghwa,Kwon, Youngjoo
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- Design, synthesis, and in vitro hMAO-B inhibitory evaluation of some 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles
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A series of 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (3a-k and 4a-u) were designed, synthesized, and evaluated for their inhibitory efficacy towards the two hMAO isoforms. Most of the derivatives were found to be potent and selective hMAO-B inhibitors. In particular, derivative 3g showed greater hMAO-B affinity than selective inhibitor selegiline coupled with high selectivity index (SI = 145). The most selective hMAO-B inhibitor was the 3-methyl analogue 3f with an SI higher than 909.
- Fioravanti, Rossella,Desideri, Nicoletta,Biava, Mariangela,Proietti Monaco, Luca,Grammatica, Laura,Yá?ez, Matilde
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p. 5128 - 5130
(2013/09/12)
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- FLAVONOID PPAR AGONISTS
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The present invention relates to PPAR agonists, and their use in therapy including the treatment of disease. In particular, the invention relates to flavonoid compounds which are PPAR-gamma agonists and/or PPAR alpha/gamma dual agonists.
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Page/Page column 36; 55-56
(2009/04/25)
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- Chalcones: A valid scaffold for monoamine oxidases inhibitors
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A large series of substituted chalcones have been synthesized and tested in vitro for their ability to inhibit human monoamine oxidases A and B (hMAO-A and hMAO-B). While all the compounds showed hMAO-B selective activity in the micro- and nanomolar ranges, the best results were obtained in the presence of chlorine and hydroxyl or methoxyl substituents. To better understand the enzyme-inhibitor interaction and to explain the selectivity of the most active compounds toward hMAO-B, molecular modeling studies were carried out on new, high resolution, hMAO-B crystallographic structures. For the only compound that also showed activity against hMAO-A as well as low selectivity, the molecular modeling study was also performed on the hMAO-A crystallographic structure. The docking technique provided new insight on the inhibition mechanism and the rational drug design of more potent/selective hMAO inhibitors based on the chalcone scaffold.
- Chimenti, Franco,Fioravanti, Rossella,Bolasco, Adriana,Chimenti, Paola,Secci, Daniela,Rossi, Francesca,Yá?ez, Matilde,Orallo, Francisco,Ortuso, Francesco,Alcaro, Stefano
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experimental part
p. 2818 - 2824
(2010/01/16)
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- 7-Hydroxy-benzopyran-4-one derivatives: A novel pharmacophore of peroxisome proliferator-activated receptor α and -γ (PPARα and γ) dual agonists
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Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARα and γ agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure of both fibrates and thiazolidinediones. New lead PPAR ligands were identified from "natraceuticals" and synthetic analogues. In total, 77 molecules, including chalcones, flavones, flavanones, isoflavones, and pyrazole derivatives, were screened and structure-activity relationship studies of the dual agonists undertaken. Compounds 68, 70, 72, and 76 were identified as novel and potent dual PPARα and γ agonists. These novel molecules may have the potential to be the future leads in PPAR-related disorders, including type II diabetes mellitus and metabolic syndrome. 2009 American Chemical Society.
- Matin, Azadeh,Gavande, Navnath,Kim, Moon S.,Yang, Nancy X.,Salam, Noeris K.,Hanrahan, Jane R.,Roubin, Rebecca H.,Hibbs, David E.
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experimental part
p. 6835 - 6850
(2010/04/04)
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- Practical and efficient entry to isoflavones by Pd(0)/C-mediated Suzuki-Miyaura reaction. Total synthesis of geranylated isoflavones
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A scalable synthesis of isoflavones taking advantage of the Suzuki-Miyaura reaction catalyzed by Pd(0)/C is described. The approach developed has been extended to the total synthesis of 7-O-geranylformononetin, griffonianone D, and conrauinone D, which did not display cytotoxicity against human HeLa carcinoma cells. In addition, this study established unambiguously the absolute configuration of natural griffonianone D.
- Felpin, Fran?ois-Xavier,Lory, Cécile,Sow, Hawaa,Acherar, Samir
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p. 3010 - 3016
(2007/10/03)
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- Synthesis of Abyssinone II and related compounds as potential chemopreventive agents
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A facile and efficient approach to the synthesis of prenylated flavonoids as potential chemopreventive agents has been described. This features the synthesis of prenyl halide, prenylation of p-hydroxybenzaldehyde, formation of prenylated polyhydroxychalco
- Moriarty, Robert M.,Grubjesic, Simonida,Surve, Bhushan C.,Chandersekera, Susantha N.,Prakash, Om,Naithani, Rajesh
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p. 263 - 267
(2007/10/03)
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- Synthesis and in vitro selective anti-Helicobacter pylori activity of pyrazoline derivatives
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In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 μg/mL MIC range.
- Chimenti,Bizzarri,Manna,Bolasco,Secci,Chimenti,Granese,Rivanera,Lilli,Scaltrito,Brenciaglia
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p. 603 - 607
(2007/10/03)
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- Synthesis of some pyrazole derivatives and preliminary investigation of their affinity binding to P-glycoprotein
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A series of substituted pyrazolines were synthesized and evaluated for their anticancer activity and for their ability to inhibit P-glycoprotein- mediated multidrug resistance by direct binding to a purified protein domain containing an ATP-binding site and a modulator interacting region. Compounds 2a and e have been found to bind to P-glycoprotein with greater affinity.
- Manna, Fedele,Chimenti, Franco,Fioravanti, Rossella,Bolasco, Adriana,Secci, Daniela,Chimenti, Paola,Ferlini, Cristiano,Scambia, Giovanni
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p. 4632 - 4635
(2007/10/03)
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- Synthesis and Selective Inhibitory Activity of 1-Acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole Derivatives against Monoamine Oxidase
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A novel series of 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives 1 - 12 have been synthesized and investigated for the ability to selectively inhibit the activity of the A and B isoforms of monoamine oxidase
- Chimenti, Franco,Bolasco, Adriana,Manna, Fedele,Secci, Daniela,Chimenti, Paola,Befani, Olivia,Turini, Paola,Giovannini, Valentina,Mondovì, Bruno,Cirilli, Roberto,La Torre, Francesco
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p. 2071 - 2074
(2007/10/03)
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- 4-Thio coumarins
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4-thio substituted coumarin derivatives and coumarin dimers are provided, as well as processes for their preparation. A synthetic process for the preparation of 4-thio substituted coumarin derivatives is provided using mild reaction conditions, which main
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Page/Page column 16-17
(2010/02/05)
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- Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: Synthesis, biological evaluation, and molecular modeling
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Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran- 2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2,4- dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1,3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an 'accessory' region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.
- Artico, Marino,Santo, Roberte Di,Costi, Roberta,Novellino, Ettore,Greco, Giovanni,Massa, Silvio,Tramontano, Enzo,Marongiu, Maria E.,De Montis, Antonella,Colla, Paolo La
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p. 3948 - 3960
(2007/10/03)
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- Synthesis and activity of a new series of chalcones as aldose reductase inhibitors
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A new series of chalcone derivatives has been synthesized and tested in vitro in order to assess their ability to inhibit aldose reductase enzyme (ALR2) and their specificity towards the target enzyme with respect to other oxidoreductases, such as aldehyde reductase, sorbitol dehydrogenase, and glutathione reductase. All the compounds display affinity for ALR2. The X-ray crystal structure of 1-(2,4-dihydroxyphenyl)-3-(2-methoxyphenyl)propen-1-one was determined.
- Severi, Fabio,Benvenuti, Stefania,Costantino, Luca,Vampa, Gabriella,Melegari, Michele,Antolini, Luciano
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p. 859 - 866
(2007/10/03)
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- Synthesis and description of chalcone-like compounds, inhibitors of aldose reductase
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A series of hydroxy- and hydroxy-methoxychalcones was synthesized and the inhibitory activity and selectivity of the compounds towards bovine lens aldose reductase (AR) were tested. All the compounds display affinity for AR. The most active proved to be 1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl)propen-1-one (isoliquiritigenin, IC50= 7.60 μM). The selectivity of this compound was also tested, its inhibitory activity being assayed against glutathione reductase and sorbitol dehydrogenase.
- Severi,Costantino,Benvenuti,Vampa,Mucci
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p. 128 - 136
(2007/10/03)
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