共查询到20条相似文献,搜索用时 15 毫秒
1.
Abhinav Kumar Rajendra Prasad G. Kociok-Köhn Kieran C. Molloy Nanhai Singh 《Inorganic chemistry communications》2009,12(7):686-690
Title compound[(n-Bu)2Sn-μ-O-μ-OH-Sn(n-Bu)2(CH3CO2)]2 was obtained accidentally by the reaction of n-Bu2SnCl2 with the metalloligand K2[Ni(CDC)2] in ethanol - water mixture while synthesizing a heterobimetallic complex [n-Bu2Sn Ni(CDC)2]. This has been characterized by micro analysis, UV–Vis, 1H, 13C and 119Sn NMR spectroscopy and the single crystal X-ray. The complex forms an interesting supramolecular architecture via (acetate)O?HO hydrogen bonding interactions which generates hydrophobic “pseudo-cage”. The electronic absorption bands of the title complex were assigned with the help of the time dependent density functional theory (TD-DFT) calculations. Density functional theory (DFT) calculations have been performed at the optimized molecular geometry of some of its putative derivatives e. g. trans p-amino cinnamic acid derivative 2; trans p-amino cinnamic acid and trans p-nitro cinnamic acid derivative 3; trans p-amino cinnamic acid and trans p-(N,N dimethylamino) cinnamic acid derivative 4. The first static hyperpolarizability (β) of the title compound and its derivatives were calculated with double numerical differentiation of total energies. The derivatives 3 and 4 showed three times and five times enhancement in the non-linear optical (NLO) responses than the standard p-nitroaniline (pNA). 相似文献
2.
Rocamora-Reverte L Carrasco-García E Ceballos-Torres J Prashar S Kaluđerović GN Ferragut JA Gómez-Ruiz S 《ChemMedChem》2012,7(2):301-310
A group of organotin(IV) complexes were prepared: [SnCy3(DMNI)] ( 1 ), [SnCy3(BZDO)] ( 2 ), [SnCy3(DMFU)] ( 3 ), and [SnPh2(BZDO)2] ( 4 ), for which DMNIH=2,6‐dimethoxynicotinic acid, BZDOH=1,4‐benzodioxane‐6‐carboxylic acid, and DMFUH=2,5‐dimethyl‐3‐furoic acid. The cytotoxic activities of compounds 1 – 4 were tested against pancreatic carcinoma (PANC‐1), erythroleukemia (K562), and two glioblastoma multiform (U87 and LN‐229) human cell lines; they show very high antiproliferative activity, with IC50 values in the 150–700 nM range after incubation for 72 h. Distribution of cellular DNA upon treatment with 1 – 4 revealed that whereas compounds 1 – 3 induce apoptosis in most of the cell lines, compound 4 does not affect cell viability in any cell line tested, indicating a possible difference in cytotoxic mechanism. Studies with the daunomycin‐resistant K562/R cell line expressing P‐glycoprotein (Pgp) showed that compounds 1 – 4 are not substrates of this protein efflux pump, indicating that these compounds do not induce acquisition of multidrug resistance, which is associated with the overexpression of Pgp. 相似文献
3.
A C18 1-pyrroline fatty ester, methyl 8-(5-hexyl-2-pyrrolin-1-yl)octanoate (1), was prepared from methyliso-ricinoleate. The C=N bond of the pyrroline ring was oxidized bym-chloroperoxy-benzoic acid to yield a mixture of oxaziridine isomers 2a,2b, which decomposed during gas chromatographic analysis
to a 2,5-disubstituted pyrrole derivative, methyl 8-(5-hexyl-1H-pyrrole-2-)octanoate (3). Compound 3 was also obtained by reaction of 2a,2b with dilute HCl in methanol. Reaction of compound
1 with iodo-methane formed anN-methyl iminium iodide intermediate 4, which on reduction with sodium borohydride furnished a mixture ofcis/trans-N-methyl-2,5-disubstituted pyrrolidine derivatives, methyl 8-(cis/trans-5-hexyl-N-methyl-pyrrolidine-2-)octanoates 5a,5b. Reduction of compound 1 with NaBH4 gave a mixture ofcis/trans-isomers of 2,5-disubstituted pyrrolidine derivatives, methyl 8-(5-hexyl-pyrrolidine-2-)octanoates 6a,6b. Acetylation of compounds
6a,6b with acetic anhydride furnished the correspondingN-acetyl pyrrolidines 7a,7b. When compound 1 was treated with perchloric acid, the corresponding iminium perchlorate derivative,
methyl 8-(5-hexyl-1-pyrrolinium perchlorate-2-)octanoate 8 was obtained. The structures of the various derivatives were characterized
by a combination of chromatographic, mass spectral and spectroscopic techniques. 相似文献
4.
Haider N. Sultani Ibrahim Morgan Hidayat Hussain Andreas H. Roos Haleh H. Haeri Goran N. Kaluerovi Dariush Hinderberger Bernhard Westermann 《International journal of molecular sciences》2021,22(13)
Multicomponent reactions, especially the Ugi-four component reaction (U-4CR), provide powerful protocols to efficiently access compounds having potent biological and pharmacological effects. Thus, a diverse library of betulinic acid (BA), fusidic acid (FA), cholic acid (CA) conjugates with TEMPO (nitroxide) have been prepared using this approach, which also makes them applicable in electron paramagnetic resonance (EPR) spectroscopy. Moreover, convertible amide modified spin-labelled fusidic acid derivatives were selected for post-Ugi modification utilizing a wide range of reaction conditions which kept the paramagnetic center intact. The nitroxide labelled betulinic acid analogue 6 possesses cytotoxic effects towards two investigated cell lines: prostate cancer PC3 (IC50 7.4 ± 0.7 μM) and colon cancer HT29 (IC50 9.0 ± 0.4 μM). Notably, spin-labelled fusidic acid derivative 8 acts strongly against these two cancer cell lines (PC3: IC50 6.0 ± 1.1 μM; HT29: IC50 7.4 ± 0.6 μM). Additionally, another fusidic acid analogue 9 was also found to be active towards HT29 with IC50 7.0 ± 0.3 μM (CV). Studies on the mode of action revealed that compound 8 increased the level of caspase-3 significantly which clearly indicates induction of apoptosis by activation of the caspase pathway. Furthermore, the exclusive mitochondria targeting of compound 18 was successfully achieved, since mitochondria are the major source of ROS generation. 相似文献
5.
Reaction of a C18 furanoic fatty acid with dimethyl dicarboxylate (DMAD) furnished the corresponding bicyclo Diels-Alder adduct, which was
partially hydrogenated over Pd/BaSO4. Heat treatment (160–180°C) of the partially hydrogenated product caused a retro-Diels-Alder reaction to yield a furanoid
fatty acid derivative containing methoxycarbonyl (COOCH3) substituents at the 3-and 4-positions of the furan nucleus. Reduction of the COOCH3 substituents with LiBH4 gave the corresponding CH2OH-substituted furanoid fatty acid. Hydrogenation of the latter over Pd/C furnished the desired dimethyl-substituted furanoid
acid derivative (overall yield 60%). The spectroscopic properties of the intermediates and product are reported. 相似文献
6.
Hans D. Schick Wolfgang E. Berdel Michael Fromm Ulrich Fink Ulrich Jehn Kurt Ulm Anneliese Reichert Hansjörg Eibl Clemens Unger Johann Rastetter 《Lipids》1987,22(11):904-910
The effects of 2-lysophosphatidylcholine (2-LPC), the alkyl lysophospholipid derivatives (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) and 1-O-hexadecyl-sn-glycero-3-phospho-trimethyl-ammonio-hexanol, the 2-acetamide analog of platelet-activating factor (PAF) 1-O-octadecyl-2-acetamide-sn-glycero-3-phosphocholine, the thioether lysophospholipid derivative (TLP) BM 41.440 and the ether-linked lipoidal amine CP-46,665 on tritiated thymidine uptake and trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human leukemias. In both assay systems, a dose range of 1–20 μg/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells. The trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness: ET-18-OCH3>BM41.440>2-acetamide analog of PAF. CP-46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 μg/ml. The trimethyl-ammoniohexanol compound showed only minor activity in the majority of tests, when added at concentrations <20 μg/ml. 2-LPC was rather ineffective. The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET-18-OCH3 and, sometimes, within the dose time frame tested of BM 41.440. All compounds tested except 2-LPC and the trimethyl-ammonio-hexanol compound were active also in this assay (inhibition of uptake>50% of the controls). Based on these results, ET-18-OCH3 and BM 41.440 are recommended for experimental bone marrow purging. 相似文献
7.
Frank-Gerrit Klrner Ulrike Kalthof Joachim Gante 《Advanced Synthesis \u0026amp; Catalysis》1997,339(1):359-364
From the pressure-induced rate enhancement the activation volume of the peptide coupling 1 with the sodium salt of glycine 2 leading to the corresponding dipeptide derivative 3 was determined to be strongly negative (ΔV≠ = −(19.3 ± 0.5) cm3mol−1 at 51.7 °C, CH3OH). This finding indicates that and association with the developing of charge proceeds in the rate-determining transition state. The pressure-induced peptide coupling was exploited to synthesize a derivative ( 12a, b ) of glutathione (γ-Glu-Cys-Gly), a biologically important tripeptide, starting from either glycine or glutamic acid. 相似文献
8.
In this research, the effects of different kinds of nucleating agents on the crystallization and mechanical properties of polyoxymethylene (POM) were studied, including inorganic, organic, and polymer nucleating agents and their compounds. These properties showed that nanoCaCO3, sorbitol derivative TMB-5, polyamide PA-4, and compound C-1/polyamide (PA)-4 can make spherulites of POM finer and more perfect, and effectively improve its notched impact toughness, in which the compound C-1/PA-4 displayed more remarkable nucleation effect. The study on the nonisothermal crystallization of POM showed that the crystallization temperature and crystallization growth rate of POM increased when C-1/PA-4 was added. The isothermal crystallization kinetics were also analyzed by the Avrami equation. The addition of C-1/PA-4 can increase the values of the Avrami exponent (n) and crystallization rate constant (k), and reduce the half-time of isothermal crystallization, t1/2, and the time corresponding to the maximum rate of crystallization, tP, indicating its remarkable nucleating effect on POM. 相似文献
9.
Xi-Shi Tai Wen-Hua Zhao 《Journal of Inorganic and Organometallic Polymers and Materials》2013,23(6):1354-1357
A novel Ca(II) coordination polymer, [CaL(H2O)2] n (L = 1,5-naphthalenedisulfonate), was synthesized by reaction of calcium perchlorate with 1,5-naphthalenedisulfonic acid sodium in CH3CH2OH/H2O. It was characterized by elemental analysis, IR, 1HNMR and thermal analysis. X-ray crystallographic reveals that the Ca(II) coordination polymer belongs to triclinic system, with space group P-1. The geometry of the Ca(II) ion is a distorted CaO6 octahedron coordination environment, arising from its coordination by two water molecules, and four oxygen atoms from two l ligands. The Ca(II) ions are linked through the O atoms of 1,5-naphthalenedisulfonate ligands to form 1D chain structure. And then a 2D layered structure is constructed by hydrogen bonds and π–π stacking. The antitumor activity of 1,5-naphthalenedisulfonic acid sodium ligand and its Ca(II) coordination polymer against human hepatoma smmc-7721 cell line and human lung adenocarcinoma A549 cell line have been investigated. 相似文献
10.
Jun-Jie Shi Dr. Kun-Hang Jia Dr. Hao Sun Dr. Hendra Gunosewoyo Prof. Fan Yang Prof. Jie Tang Prof. Jian Luo Prof. Li-Fang Yu 《ChemMedChem》2021,16(3):524-536
Since its initial discovery as the basis for nicotinic acetylcholine receptor ligands, the 3-alkoxyisoxazole scaffold has been shown to be a versatile platform for the development of potent σ1 and σ2 receptor ligands. Herein we report a further SAR exploration of the 3-alkoxyisoxazole scaffold with the aim of obtaining potent σ2 receptor ligands. Various substitutions on the benzene ring and at the basic amino regions resulted in a total of 21 compounds that were tested for their binding affinities for the σ2 receptor. In particular, compound 51 [(2S)-1-(4-ammoniobutyl)-2-(((5-((3,4-dichlorophenoxy)methyl)isoxazol-3-yl)oxy)methyl)pyrrolidin-1-ium chloride] was identified as one of the most potent σ2 ligands within the series, with a Ki value of 7.9 nM. It demonstrated potent antiproliferative effects on both osteosarcoma cell lines 143B and MOS−J (IC50 values of 0.89 and 0.71 μM, respectively), relative to siramesine (IC50 values of 1.81 and 2.01 μM). Moreover, compound 51 inhibited clonal formation of osteosarcoma 143B cells at 1 μM, corresponding to half the dose required of siramesine for similar effects. The general cytotoxicity profile of compound 51 was assessed in a number of normal cell lines, including HaCaT, HAF, and LO2 cells. Furthermore, FACS analysis showed that compound 51 likely inhibits osteosarcoma cell growth by disruption of the cell cycle and promotion of apoptosis. 相似文献
11.
Margarita A. Gradova Oleg V. Gradov Anton V. Lobanov Anna V. Bychkova Elena D. Nikolskaya Nikita G. Yabbarov Mariia R. Mollaeva Anton E. Egorov Alexey A. Kostyukov Vladimir A. Kuzmin Irina S. Khudyaeva Dmitry V. Belykh 《International journal of molecular sciences》2023,24(1)
A novel amphiphilic cationic chlorin e6 derivative was investigated as a promising photosensitizer for photodynamic therapy. Two cationic –N(CH3)3+ groups on the periphery of the macrocycle provide additional hydrophilization of the molecule and ensure its electrostatic binding to the mitochondrial membranes and bacterial cell walls. The presence of a hydrophobic phytol residue in the same molecule results in its increased affinity towards the phospholipid membranes while decreasing its stability towards aggregation in aqueous media. In organic media, this chlorin e6 derivative is characterized by a singlet oxygen quantum yield of 55%. Solubilization studies in different polymer- and surfactant-based supramolecular systems revealed the effective stabilization of this compound in a photoactive monomolecular form in micellar nonionic surfactant solutions, including Tween-80 and Cremophor EL. A novel cationic chlorin e6 derivative also demonstrates effective binding towards serum albumin, which enhances its bioavailability and promotes effective accumulation within the target tissues. Laser confocal scanning microscopy demonstrates the rapid intracellular accumulation and distribution of this compound throughout the cells. Together with low dark toxicity and a rather good photostability, this compound demonstrates significant phototoxicity against HeLa cells causing cellular damage most likely through reactive oxygen species generation. These results demonstrate a high potential of this derivative for application in photodynamic therapy. 相似文献
12.
Prof. Dr. Zhe Li Prof. Dr. Satish Rao Prof. Dr. Joel R. Gever Clifford Bryant Dr. Alejandra Gallardo‐Godoy Dr. Elena Dolghih Kartika Widjaja Manuel Elepano Prof. Dr. Matthew P. Jacobson Prof. Dr. Stanley B. Prusiner Prof. Dr. Adam R. Renslo 《ChemMedChem》2013,8(5):847-857
Recently, we described the aminothiazole lead (4‐biphenyl‐4‐ylthiazol‐2‐yl)‐(6‐methylpyridin‐2‐yl)‐amine ( 1 ), which exhibits many desirable properties, including excellent stability in liver microsomes, oral bioavailability of ~40 %, and high exposure in the brains of mice. Despite its good pharmacokinetic properties, compound 1 exhibited only modest potency in mouse neuroblastoma cells overexpressing the disease‐causing prion protein PrPSc. Accordingly, we sought to identify analogues of 1 with improved antiprion potency in ScN2a‐cl3 cells while retaining similar or superior properties. Herein we report the discovery of improved lead compounds such as (6‐methylpyridin‐2‐yl)‐[4‐(4‐pyridin‐3‐yl‐phenyl)thiazol‐2‐yl]amine and cyclopropanecarboxylic acid (4‐biphenylthiazol‐2‐yl)amide, which exhibit brain exposure/EC50 ratios at least tenfold greater than that of compound 1 . 相似文献
13.
Shadpour E Mallakpour Abdol-Reza Hajipour Ali-Reza Mahdavian Fatemeh Rafiemanzelat 《Polymer International》1999,48(2):109-116
Cis -9,10-dihydro-9,10-ethanoanthracene-11-12-dicarboxylic acid anhydride (1) was converted into its amic acid derivative by reaction with L -leucine. The cyclization reaction was carried out in situ using triethylamine to give the succinic imide-acid derivative (2). Compound (2) was converted to the acid chloride (3) by reaction with thionyl chloride. The reaction of acid chloride (3) with isoeugenol (4) was carried out in chloroform and a novel optically active isoeugenol ester derivative (5) was obtained in high yield. 4-Phenyl-1,2,4-triazoline-3,5-dione (PhTD) (6) was allowed to react with compound (5). The reaction is very fast and gives only one diastereoisomer of (7) via Diels–Alder and ene pathways in quantitative yield. Compound (7) was characterized by 1H NMR, IR, specific rotation and elemental analysis, and was used as a model for the polymerization reactions. The polymerization reactions of compound (5) with bis-triazolinediones (8), (9) were performed in N,N-dimethylacetamide (DMAc) at room temperature. The reactions are exothermic and fast, and give novel optically active polymers. Some physical properties and structural characterizations of these new polymers have been studied, and are reported. © 1999 Society of Chemical Industry 相似文献
14.
Bauer JB Lippert WP Dörrich S Tebbe D Burschka C Christie VB Tams DM Henderson AP Murray BA Marder TB Przyborski SA Tacke R 《ChemMedChem》2011,6(8):1509-1517
Twofold sila‐substitution (C/Si exchange) of the clinically used RXR‐selective retinoid agonist bexarotene leads to disila‐bexarotene, which displays pharmacological potency similar to that of the parent carbon compound, as shown in a HeLa‐cell‐based RXR assay. Formal exchange of the SiCH2CH2Si group in disila‐bexarotene with a SiCH2Si or SiOSi moiety leads to the disila‐bexarotene analogues 8 and 9 . The silicon compounds 8 and 9 were synthesized in multistep syntheses, starting from HC?C(CH3)2SiCH2Si(CH3)2C?CH and HC?C(CH3)2SiOSi(CH3)2C?CH, respectively. The key step in the syntheses of 8 and 9 is a cobalt‐catalyzed [2+2+2] cycloaddition reaction that affords the 1,3‐disilaindane and 2‐oxa‐1,3‐disilaindane skeletons. Disila‐bexarotene and its analogues 8 and 9 were studied for their biological effects relative to all‐trans retinoic acid in cultured human pluripotent stem cells. The parent carbon compound bexarotene was included in some of these biological studies. Although the silicon‐containing bexarotene analogues disila‐bexarotene, 8 , and 9 appear not to regulate the differentiation of TERA2.cl.SP12 stem cells, preliminary evidence indicates that these compounds may possess enhanced functions over the parent compound bexarotene, such as induction and regulation of cell death and cell numbers. The biological data obtained indicate that bexarotene, contrary to the silicon‐containing analogues disila‐bexarotene, 8 , and 9 , may partially act to induce cell differentiation. 相似文献
15.
Lidia Ciccone Eugenia Piragine Simone Brogi Caterina Camodeca Raffaele Fucci Vincenzo Calderone Susanna Nencetti Alma Martelli Elisabetta Orlandini 《International journal of molecular sciences》2022,23(23)
The sirtuin 1 (SIRT1) activator resveratrol has emerged as a promising candidate for the prevention of vascular oxidative stress, which is a trigger for endothelial dysfunction. However, its clinical use is limited by low oral bioavailability. In this work, we have applied a previously developed computational protocol to identify the most promising derivatives from our in-house chemical library of resveratrol derivatives. The most promising compounds in terms of SIRT1 activation and oral bioavailability, predicted in silico, were evaluated for their ability to activate the isolated SIRT1 enzyme. Then, we assessed the antioxidant effects of the most effective derivative, compound 3d, in human umbilical vein endothelial cells (HUVECs) injured with H2O2 100 µM. The SIRT1 activator 3d significantly preserved cell viability and prevented an intracellular reactive oxygen species increase in HUVECs exposed to the oxidative stimulus. Such effects were partially reduced in the presence of a sirtuin inhibitor, sirtinol, confirming the potential role of sirtuins in the activity of resveratrol and its derivatives. Although 3d appeared less effective than resveratrol in activating the isolated enzyme, the effects exhibited by both compounds in HUVECs were almost superimposable, suggesting a higher ability of 3d to cross cell membranes and activate the intracellular target SIRT1. 相似文献
16.
The novel tetrasubstituted metal-free phthalocyanine and metallophthalocyanines 7, bearing four 13-membered diazadithia macrocycle moieties at peripheral positions were synthesized by cyclotetramerization of the corresponding phthalonitrile derivative in a multi-step reaction sequence. The metal-free phthalocyanine was synthesized by microwave irradiation of the corresponding dicyano compound in 2-(dimethylamino)ethanol for 10 min. Metallophthalocyanines were obtained from the respective dicyano derivative and corresponding anhydrous metal salts NiCl2 and ZnCl2, CoCl2, CuCl2, respectively, by microwave irradiation in 2-(dimethylamino)ethanol at 175 °C, 350 W for 10 min. The new compounds were characterized by a combination of IR, 1H NMR, 13C NMR, UV–vis, elemental analysis and MS spectral data. 相似文献
17.
Prof. Kenneth K. Laali Angela T. Zwarycz Prof. Scott D. Bunge Dr. Gabriela L. Borosky Dr. Manabu Nukaya Prof. Gregory D. Kennedy 《ChemMedChem》2019,14(12):1173-1184
A series of deuterated curcuminoids (CUR) were synthesized, bearing two to six OCD3 groups, in some cases in combination with methoxy groups, and in others together with fluorine or chlorine atoms. A model ring-deuterated hexamethoxy-CUR–BF2 and its corresponding CUR compound were also synthesized from a 2,4,6-trimethoxybenzaldehyde-3,5-d2 precursor. As with their protio analogues, the deuterated compounds were found to remain exclusively in the enolic form. The antiproliferative activities of these compounds were studied by in vitro bioassays against a panel of 60 cancer cell lines, and more specifically in human colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, and Caco2) and in normal colon cells (CCD841CoN). The deuterated CUR–BF2 adducts exhibited better overall growth inhibition by NCI-60 assay, while for other CUR–BF2 adducts the non-deuterated analogues were more cytotoxic. Results of the more focused comparative cell viability assays followed the same trend, but with some variation depending on cell lines. The CUR–BF2 adducts exhibited significantly higher cytotoxicity than CURs. Structural studies (X-ray and DFT) and computational molecular docking calculations comparing their inhibitory efficacy with those of known anticancer agents used in chemotherapy are also reported. 相似文献
18.
Anticancer Gold(III) Peptidomimetics: From Synthesis to in vitro and ex vivo Biological Evaluations
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Dr. Giulia Boscutti Dr. Chiara Nardon Prof. Luciano Marchiò Dr. Marco Crisma Dr. Barbara Biondi Daniele Dalzoppo Lisa Dalla Via Prof. Fernando Formaggio Prof. Angela Casini Prof. Dolores Fregona 《ChemMedChem》2018,13(11):1131-1145
Five new AuIII‐peptidodithiocarbamato complexes of the type [AuIIIBr2(dtc‐AA1‐AA2‐OR] (in which AA1=N‐methylglycine (Sar), l /d ‐Pro; AA2=l /d ‐Ala, α‐aminoisobutyric acid (Aib); R=OtBu, triethylene glycol methyl ether), differing with regard to the amino acid sequence and/or the chiral amino acid configuration, were designed to enhance tumor selectivity and bioavailability. The gold(III)‐based moiety was functionalized to exploit the targeting properties of the peptidomimetic ligand toward two peptide transporters (namely PEPT1 and PEPT2), which are upregulated in several tumor cells. The compounds were synthesized and fully characterized, mainly by means of elemental analysis, one‐ and two‐dimensional NMR spectroscopy, FT‐IR, and UV/Vis spectrophotometry. The crystal structures of three compounds were also solved by X‐ray diffraction. In vitro cytotoxicity studies using a panel of human tumor cell lines (A549 [non‐small‐cell lung carcinoma], MCF‐7 [breast cancer], A2780 [ovarian carcinoma], H1975 [non‐small‐cell lung carcinoma], H460 [large‐cell lung carcinoma], and A431 [human epidermoid carcinoma]) showed the dtc‐Pro‐Aib‐OtBu derivative to be very effective, with GI50 values much lower than those of cisplatin. This complex was thus selected for evaluating stability under physiological conditions and possible interactions with serum albumin, as well in PARP‐1 enzyme inhibition assays and preliminary ex vivo toxicity experiments on healthy rat tissues. 相似文献
19.
Simona Dedoni Luisa Marras Maria C. Olianas Angela Ingianni Pierluigi Onali 《International journal of molecular sciences》2021,22(15)
Neurotrophins and their receptors are relevant factors in controlling neuroblastoma growth and progression. The histone deacetylase (HDAC) inhibitor valproic acid (VPA) has been shown to downregulate TrkB and upregulate the p75NTR/sortilin receptor complex. In the present study, we investigated the VPA effect on the expression of the neurotrophin-3 (NT-3) receptor TrkC, a favorable prognostic marker of neuroblastoma. We found that VPA induced the expression of both full-length and truncated (TrkC-T1) isoforms of TrkC in human neuroblastoma cell lines without (SH-SY5Y) and with (Kelly, BE(2)-C and IMR 32) MYCN amplification. VPA enhanced cell surface expression of the receptor and increased Akt and ERK1/2 activation by NT-3. The HDAC inhibitors entinostat, romidepsin and vorinostat also increased TrkC in SH-SY5Y, Kelly and BE(2)-C but not IMR 32 cells. TrkC upregulation by VPA involved induction of RUNX3, stimulation of ERK1/2 and JNK, and ERK1/2-mediated Egr1 expression. In SH-SY5Y cell monolayers and spheroids the exposure to NT-3 enhanced the apoptotic cascade triggered by VPA. Gene silencing of both TrkC-T1 and p75NTR prevented the NT-3 proapoptotic effect. Moreover, NT-3 enhanced p75NTR/TrkC-T1 co-immunoprecipitation. The results indicate that VPA upregulates TrkC by activating epigenetic mechanisms and signaling pathways, and sensitizes neuroblastoma cells to NT-3-induced apoptosis. 相似文献
20.
Dr. Rosa Purgatorio Dr. Larisa N. Kulikova Dr. Leonardo Pisani Dr. Marco Catto Dr. Modesto de Candia Prof. Antonio Carrieri Prof. Saverio Cellamare Dr. Annalisa De Palma Andrey A. Beloglazkin Ghulam Reza Raesi Prof. Leonid G. Voskressensky Prof. Cosimo D. Altomare 《ChemMedChem》2020,15(20):1947-1955
A number of 1,2,3,4-tetrahydrochromeno[3,2-c]pyridin-10-one derivatives have been synthesized and screened against different targets involved in the onset and progression of Alzheimer's disease (AD), such as acetyl- and butyrylcholinesterase (AChE and BChE), monoamine oxidases A and B (MAO A and B), aggregation of β-amyloid (Aβ) and reactive oxygen species (ROS) production. Derivatives 1 c , 3 b , 4 and 5 a showed multifaceted profiles of promising anti-AD features and returned well-balanced multitargeting inhibitory activities. Moreover, compound 1 f , a potent and selective human MAO B inhibitor (IC50=0.89 μM), proved to be a safe neuroprotectant in a human neuroblastoma cell line (SH-SY5Y) by improving viability impaired by Aβ1–42 and pro-oxidant insult. Furthermore, structure–activity relationships (SARs) and docking models were derived in order to assist further hit-to-lead optimization stage. 相似文献