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1.
One major field of interest in bioinorganic chemistry is the design and synthesis of inorganic compounds with low molecular mass, showing structural, spectroscopic, and reactivity properties that mimic enzymes, such as purple acid phosphatases (PAPs). In this study, the unsymmetrical heptadentate ligand 2-[(4,7-diisopropyl-1,4,7-triazacyclonon-1-yl)methyl]-6-{[(2-hydroxybenzyl)(pyridin-2-ylmethyl)-amino]methyl}-4-methylphenol (H(2) L) and its first mixed-valence complex [Fe(III) Zn(II) (L)(μ-OAc)(2) ]ClO(4) (1) were synthesized. Physical and chemical measurements (crystal structure, conductometry, IR and UV/VIS spectroscopy, and electrochemistry) were performed for 1, and these properties are compared with those presented by the kbPAPs active sites. Potentiometric titration studies of 1 have confirmed its acid/base properties that are crucial for the understanding of the phosphodiester and DNA catalytic cleavage in future studies. 相似文献
2.
4'-Azaflavone (=2-(pyridin-4-yl)-4H-1-benzopyran-4-one; 4) and 3-[(pyridin-4-yl)methyl]-4'-azaflavone (5) were synthesized by a simple environmentally friendly microwave-assisted one-pot method through the cyclization of 3-hydroxy-1-(2-hydroxyphenyl)-3-(pyridin-4-yl)propan-1-one (1), (E)-2'-hydroxy-4-azachalcone (2; chalcone=1,3-diphenylprop-2-en-1-one), and 2'-hydroxy-2-[(hydroxy)(pyridin-4-yl)methyl]-4'-azachalcone (3) under solventless conditions using silica-supported NaHSO(4), followed by treatment with base. In addition, N-alkyl-substituted 4'-azaflavonium bromides 6 and 7 were prepared from compounds 4 and 5, respectively. The antimicrobial and antioxidant activities of compounds 1-7 were tested. The N-alkyl-substituted 4'-azaflavonium bromides 6 and 7 showed high antimicrobial activity against the Gram-positive bacteria and the fungus tested, with MIC values close to those of reference antimicrobials ampicilline and fluconazole. The alkylated compounds 6 and 7 also showed a good antioxidant character in the two antioxidant methods, DPPH (=1,1-diphenyl-2-picrylhydrazyl) radical-scavenging and ferric reducing/antioxidant power (FRAP) tests. 相似文献
3.
Reena Singh 《Inorganica chimica acta》2010,363(12):3131-2301
The orange-red colored complexes of the type [Fe(LSB)Cl3], 1, have been synthesized in excellent yields by reacting FeCl3·6H2O with LSB in methanol. Here, LSB is (2-(ethylthio)-N-(pyridin-2-ylmethyl)ethanamine), (LSB1) and (2-(benzylthio)-N-(pyridin-2-ylmethyl)ethanamine) (LSB2). Similarly, FeCl3·6H2O reacted with 2-(((2-(ethylthio) ethyl) (pyridin-2-ylmethyl)amino)methyl)phenol (HL1), 2-(((2-(ethylthio)ethyl)(pyridin-2 ylmethyl)amino)methyl)-4-nitrophenol (HL2), 4-chloro-2-(((2-(ethylthio)ethyl)(pyridin-2-ylmethyl)amino)methyl)phenol (HL3), 2-(((2-(benzylthio)ethyl)(pyridin-2-ylmethyl) amino)methyl)phenol (HL4), 2-(((2-(benzylthio)ethyl)(pyridin-2-ylmethyl)amino)methyl) -4-nitrophenol (HL5), and 4-chloro-2-(((2-(benzylthio)ethyl)(pyridin-2-ylmethyl)amino) methyl)phenol (HL6) to give dichloro complexes of the type [Fe(L)Cl2], 2. The solid and solution structure of the complexes, as well as their properties, were probed using X-ray diffraction, spectroscopic and electrochemical methods. The Mössbauer spectral study at 80 K for complexes reveals the existence of (III) oxidation state and high-spin state of the metal center in the complex. Dioxygenase activity of the complexes has been studied and both 1 and 2 have been found to display the intradiol-cleaving pathway. However, no extradiol cleavage products have been isolated. 相似文献
4.
The complexes [Mn(L1)(tcc)] (1), [Mn(L2)(tcc)] · H2O · 0.5CH3OH (2), [Mn(L3)(tcc)] · CH2Cl2 (3), [Mn(L4)(tcc)] · 1.5CH2Cl2 (4), [Mn(L5)(tcc)] (5), and (HN(C2H5)3)[Mn(L6)(tcc)] · CH2Cl2 (6) have been synthesized using the ligands HL1 (2-[(bis(pyridin-2-ylmethyl)amino)methyl]phenol), HL2 (2-[[((6-methylpyridin-2-yl)methyl)(pyridin-2-ylmethyl)amino]methyl] phenol), HL3 (2-[[((6-methylpyridin-2-yl)methyl)(pyridin-2-ylmethyl)amino]methyl]-4-nitrophenol), HL4 (2-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-bromophenol), HL5 (2-[(bis(pyridin-2-ylmethyl)amino)methyl]-6-methoxyphenol) and H2L6 ([(bis(2-hydroxy-5-nitrobenzyl))(pyridin-2-ylmethyl)]amine) and characterized by X-ray crystallography, mass spectrometry, IR, UV-Vis spectroscopy, cyclic voltammetry, and elemental analysis. Compounds 1 and 6 crystallize in the monoclinic space groups P21/n and P21/c, respectively, whereas the crystal structures of complexes 2, 3, and 4 were solved in the triclinic space group . Complex 5 crystallizes in the orthorhombic space group P212121. Complexes 1-6 are structural related to the proposed active site of intradiol cleaving catechol dioxygenase exhibiting a distorted octahedral N3O3 (1-5) and N2O4 (6) donor set, respectively. Complexes 1-6 can be regarded as structural manganese analogous for substituted forms of iron-containing intradiol cleaving catechol dioxygenases, where the substrate tetrachlorocatechol (tcc) is asymmetrically bound to the metal center. 相似文献
5.
Sudha Karumuri Puneet Kumar Singh Pratyoosh Shukla 《Indian journal of microbiology》2015,55(3):333-340
The diseases caused by dermatophytes are common among several other infections which cause serious threat to human health. It is evident that enzyme squalene epoxidase is responsible for prolonged dermatophyte infection and it is appealing to note that this enzyme is also responsible for fatty acid synthesis in these groups of fungi. In the present study, terbinafine drug which targets enzyme squalene epoxidase has been explored to design its various novel analogues. The present study suggests that many more prominent drug analogues could be constituted which may be crucial towards designing new drug candidates. In the present study, we have designed a series of such analogues viz. [(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)(naphthalen-1-ylmethyl)amine, N-[8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]-2-(sulfoamino) acetamide, {[4-(dihydroxyamino)-8-({[(2E)-6,6-dimethylhept-2-en-4-yn-1-yl](methyl)amino}methyl)naphthalen-1-yl]sulfanyl}methanol and (R)-{[4-({[(2E,6R)-6,7-dimethyloct-2-en-4-yn-1-yl](methyl)amino}methyl)-5-[(hydroxysulfamoyl)amino]naphthalen-1-yl]amino}sulfinic acid. Moreover, further by molecular docking approach the binding between enzyme and designed analogues was further analysed. The present preliminary report suggested a considerably good docking interaction score of −338.75 kcal/mol between terbinafine and squalene epoxidase from Trichophyton rubrum. This preliminary study implies that few designed candidate ligands can be effectual towards the activity of this enzyme and can play crucial role in pathogenesis control of T. rubrum. 相似文献
6.
Yi JW Barry NP Furrer MA Zava O Dyson PJ Therrien B Kim BH 《Bioconjugate chemistry》2012,23(3):461-471
The self-assembly of 2,4,6-tris(pyridin-4-yl)-1,3,5-triazine (tpt) triangular panels with p-cymene (pPr(i)C(6)H(4)Me) ruthenium building blocks and 2,5-dioxydo-1,4-benzoquinonato (dobq) or 5,8-dioxydo-1,4-naphthoquinonato (donq) bridges, in the presence of a pyrenyl-nucleoside derivatives (pyreneR), affords the triangular prismatic host-guest compounds [(pyrene-R)?Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(dobq)(3)](6+) ([(pyrene-R)?1](6+)) and [(pyrene-R)?Ru(6)(pPr(i)C(6)H(4)Me)(6)(tpt)(2)(donq)(3)](6+) ([(pyrene-R)?2](6+)), respectively. The inclusion of six monosubstitutedpyrenyl-nucleosides (pyrene-R1 = 5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R2 = 5-fluoro-5'-(1-pyrenyl butanoate)-2'-deoxyuridine, pyrene-R3 = 5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R4 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-glycyl}-2'-deoxyuridine, pyrene-R5 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyvuridine, pyrene-R6 = 5-fluoro-5'-{N-[1-oxo-4-(1-pyrenyl)butyl]-phenylalanyl}-2'-deoxyuridine) has been accomplished. The carceplex nature of [(pyrene-R)?1](6+) with the pyrenyl moiety firmly encapsulated in the hydrophobic cavity of the cage with the nucleoside groups pointing outward was confirmed by NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS), while the host-guest nature of [(pyrene-R)?2](6+) was studied in solution by NMR techniques. In contrast to the floxuridine compounds used in the clinic, the host-guest complexes are highly water-soluble. Consequently, the cytotoxicities of these water-soluble compounds have been established using human ovarian A2780 and A2780cisR cancer cells. All the host-guest systems are more cytotoxic than the empty cages alone [1][CF(3)SO(3)](6) (IC(50) = 23 μM) and [2][CF(3)SO(3)](6) (IC(50) = 10 μM), the most active compound [pyrene-R4?1][CF(3)SO(3)](6)being 2 orders of magnitude more cytotoxic (IC(50) = 0.3 μM) on these human ovarian cancer cell lines (A2780 and A2780cisR). 相似文献
7.
Boschelli DH Barrios Sosa AC Golas JM Boschelli F 《Bioorganic & medicinal chemistry letters》2007,17(5):1358-1361
Of a series of 7-ethynyl-3-quinolinecarbonitriles, the most potent Src inhibitory activity was observed with 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[4-(4-methylpiperazin-1-yl)but-1-ynyl]-3-quinolinecarbonitrile (SKS-927). Variation of the solubilizing amine tail or removal of the methoxy group from either C-6 of the quinoline core or C-5 of the aniline headpiece led to reduced activity. 相似文献
8.
Kaila N Green N Li HQ Hu Y Janz K Gavrin LK Thomason J Tam S Powell D Cuozzo J Hall JP Telliez JB Hsu S Nickerson-Nutter C Wang Q Lin LL 《Bioorganic & medicinal chemistry》2007,15(19):6425-6442
We have previously reported the discovery and initial SAR of the [1,7]naphthyridine-3-carbonitriles and quinoline-3-carbonitriles as Tumor Progression Loci-2 (Tpl2) kinase inhibitors. In this paper, we report new SAR efforts which have led to the identification of 4-alkylamino-[1,7]naphthyridine-3-carbonitriles. These compounds show good in vitro and in vivo activity against Tpl2 and improved pharmacokinetic properties. In addition they are highly selective for Tpl2 kinase over other kinases, for example, EGFR, MEK, MK2, and p38. Lead compound 4-cycloheptylamino-6-[(pyridin-3-ylmethyl)-amino]-[1,7]naphthyridine-3-carbonitrile (30) was efficacious in a rat model of LPS-induced TNF-alpha production. 相似文献
9.
《Bioorganic & medicinal chemistry》2020,28(5):115307
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer. 相似文献
10.
Teobaldo Cuya Arlan da Silva Gonçalves Jorge Alberto Valle da Silva Teodorico C. Ramalho Kamil Kuca 《Journal of biomolecular structure & dynamics》2013,31(13):3444-3452
The oximes 4-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HI-6) and 3-carbamoyl-1-[({2-[(E)-(hydroxyimino) methyl] pyridinium-1-yl} methoxy) methyl] pyridinium (known as HS-6) are isomers differing from each other only by the position of the carbamoyl group on the pyridine ring. However, this slight difference was verified to be responsible for big differences in the percentual of reactivation of acetylcholinesterase (AChE) inhibited by the nerve agents tabun, sarin, cyclosarin, and VX. In order to try to find out the reason for this, a computational study involving molecular docking, molecular dynamics, and binding energies calculations, was performed on the binding modes of HI-6 and HS-6 on human AChE (HssAChE) inhibited by those nerve agents. 相似文献
11.
Two new compounds, dracol (= (3R)-2,3-dihydro-3,5-dihydroxy-7-methoxy-3-[(4-methoxyphenyl)methyl]-8-methyl-4H-[1]benzopyran-4-one; 1) and icodeside (= (1beta,3beta,23S,24S)-3,23-dihydroxy-1-{[2-O-(2,3,4-tri-O-acetyl-alpha-L-rhamnopyranosyl)-alpha-L-arabinopyranosyl]oxy}spirosta-5,25(27)-dien-24-yl alpha-L-arabinopyranoside; 2), were isolated from the EtOH extract of the leaves of Dracaena draco, together with 17 known constituents. The structures of 1 and 2 were elucidated by in-depth spectroscopic analysis, and those of the known compounds were identified by comparison of their NMR and MS data with those reported in the literature. Icodeside (2) showed moderate cytotoxicity against human HL-60 and A-431 cells (Table 3). 相似文献
12.
Tomasz Ruman Karolina D?ugopolska Agata Jurkiewicz Wojciech Rode 《Bioorganic chemistry》2009,37(3):65-69
Novel boron compounds - 5,6-saturated borauracil derivatives (4-bromo-5,6-dihydroborauracil, 4-hydroxy-5,6-dihydroborauracil and 4-methoxy-5,6-dihydroborauracil) are presented along with other boron compounds obtained from N-vinylurea: N-substituted β-boronic amino acid - 2-{[(dihydroxyborano-amino)(dihydroxyboranooxy)methyl]-amino}ethylboronic acid and substituted methoxy-borane O-[(1-amino-1-N-vinylamino)methyl]dihydroxyboronate. 相似文献
13.
Dassonville A Bretéché A Evano J Duflos M le Baut G Grimaud N Petit JY 《Bioorganic & medicinal chemistry letters》2004,14(21):5441-5444
The authors have described the synthetic way to new N-pyridinyl(methyl)indolylpropanamides acting as non acidic NSAIDs. Pharmacomodulation was carried out at N-1 and C-5 of the indole ring and at the level of the propanamide chain. N-(pyridin-3-ylmethyl)-3-[5-chloro-1-(4-chlorobenzyl)-indol-3-yl]propanamide 32 represents one of the most potent compounds evaluated in the TPA-induced mouse ear swelling assay, with a level of activity higher than that of ibuprofen and comparable to that of dexamethasone. 相似文献
14.
Iryna A. Koval Mieke Huisman Eric Saint-Aman Bernt Krebs 《Inorganica chimica acta》2006,359(12):4071-4078
The new asymmetric phenol-based N,O,S-ligand Hpy2th1as was prepared by the straightforward reductive amination of 3-{[bis(pyridin-2-ylmethyl)amino]methyl}-2-hydroxybenzaldehyde with (thiophen-2-yl)methylamine. This potentially hexadentate ligand was used to coordinate to copper(II) chloride. Two dinuclear copper complexes were thus synthesised and fully characterized. Although the two coordination compounds exhibit identical complex cations, the crystal packings of both molecules significantly differ, which is most likely induced by the distinct, but geometrically related anions, namely tetrachlorocuprate(II) and perchlorate. 相似文献
15.
《Bioorganic & medicinal chemistry》2014,22(5):1736-1750
Here we describe the design, synthesis, and pharmacological evaluation of a set of compounds structurally related to the high affinity serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (6, LP-211). Specific structural modifications were performed in order to maintain affinity for the target receptor and to improve the selectivity over 5-HT1A and adrenergic α1 receptors. The synthesized compounds have chemical features that could enable labeling with a positron emitter radioisotope (carbon-11 or fluorine-18) and lipophilicity within the range considered optimal for brain penetration and low non-specific binding. 4-[2-(4-Methoxyphenyl)phenyl]-N-(pyridin-4-ylmethyl)piperazinehexanamide (23a) and N-pyridin-4-ylmethyl-3-[4-[2-(4-methoxyphenyl)phenyl]piperazin-1-yl]ethoxy]propanamide (26a) were radiolabeled on the methoxy group with carbon-11. Positron emission tomography (PET) analysis revealed that [11C]-23a and [11C]-26a were P-glycoprotein (P-gp) substrates and rapidly metabolized, resulting in poor brain uptake. These features were not predicted by in vitro tests. 相似文献
16.
Fang Li Ting-Ting Yan Ying-Ying Fu Nen-Ling Zhang Lei Wang Yan-Bing Zhang Juan Du Ji-Feng Liu 《化学与生物多样性》2021,18(4):e2001012
Chemical investigation of the ethanol extract of the branch and leaves of Illicium majus resulted in the isolation of four new phenylpropanoid glycosides ( 1 – 4 ) and one new phenolic glycoside ( 9 ), along with 13 known ones. Spectroscopic techniques were used to elucidate the structures of the new isolates such as 3-[(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-2,3-dihydro-1-benzofuran-5-yl]propyl β-D-glucopyranoside ( 1 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-glucopyranoside ( 2 ), [(2R,3S)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-2,3-dihydro-1-benzofuran-3-yl]methyl 2-O-α-L-rhamnopyranosyl-β-D-xylopyranoside ( 3 ), 3-[(2R,3S)-3-({[2-O-(4-O-acetyl-α-L-rhamnopyranosyl)-β-D-xylopyranosyl]oxy}methyl)-7-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-2,3-dihydro-1-benzofuran-5-yl]propyl acetate ( 4 ), and 4-(2-hydroxyethyl)phenyl 3-O-β-D-glucopyranosyl-β-D-glucopyranoside ( 9 ). Free radical scavenging activities of the isolates were elucidated through the DPPH assay method. The most active compounds, 1-O-caffeoyl-β-D-glucopyranose ( 17 ) and soulieana acid 1 ( 18 ), exhibited moderate radical scavenging activities (IC50=37.7±4.4 μM and IC50=97.2±3.4 μM, respectively). The antibacterial activities of the isolates against Staphylococcus aureus and Escherichia coli were also assessed, and no activity was shown at the measured concentration (<32 μg/mL). 相似文献
17.
Takuo Nishida Hiroaki Matsumae Ikuko Machida Takeji Shibatani 《Biocatalysis and Biotransformation》1995,12(3):205-214
As a result of screening of microorganisms, Mucor ambiguus IFO 6742 was found to reduce methyl 2-chloro-3-(4-methoxyphenyl)-3-oxopropionate (2) to give methyl (2S,3R)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate [(2S,3R)-3] in good yield with high enantioselectivity. The resulting (2S, 3R)-3 was converted into methyl (2S,3R)-3-(4-methoxyphenyl)glycidate [(2S,3R)-4] by treatment with sodium methoxide. On the other hand, its enantiomer, (2R,3S)-4 was obtained by the Mitsunobu esterification of (2S,3R)-3 and subsequent treatment with sodium methoxide. Also (2R,3S)-4 was obtained by the treatment of (2RS,3S)-3, which was obtained from 2 by Trichoderma viride OUT 4642, with sodium methoxide. 相似文献
18.
Four hexaazacyclophanes, 16a-d, incorporating two pyridine units and a (pyridin-2-yl)methyl or (quinolin-2-yl)methyl pendant group at one of the ring N-atoms have been prepared. The key step of the synthesis is an intermolecular cyclization of N,N-bis{[6-(tosyloxymethyl)pyridin-2-yl]methyl}-2-nitrobenzenesulfonamide (7) with either tert-butyl bis{2-[(2-nitrophenylsulfonyl)amino]ethyl}carbamate (2a) or tert-butyl bis{3-[(2-nitrophenylsulfonyl)amino]propyl}carbamate (2b) in the presence of anhydrous Cs(2)CO(3). Removal of the acid-labile tert-butoxycarbonyl protection then allows attachment of the pendant group by reductive alkylation to the exposed secondary amino group, and deprotection of the remaining aliphatic ring N-atoms completes the synthesis. The ability of the cyclophanes and their dinuclear Cu(2+) and Zn(2+) complexes to cleave the mRNA cap structure, m(7)G(5')pppG(5') (1), has been studied. 相似文献
19.
Jian-Zhong Wu Elisabeth Bouwman Allison M. Mills Jan Reedijk 《Inorganica chimica acta》2004,357(9):2694-2702
Four new ligands, N-(2-methoxyethyl)-N-(pyridin-2-ylmethyl)amine (mepma), N-(3-methoxypropyl)-N,N-bis(pyridin-2-ylmethyl)amine (mpbpa), N-(2-methoxyethyl)-N,N-bis(pyridin-2-ylmethyl)amine (mebpa) and 2-{[(2-methoxyethyl)(pyridin-2-ylmethyl)amino]methyl} phenol (Hmepap), and four of their complexes with manganese(II) halides, [MnCl2(mepma)2] (1), [MnCl(μ-Cl)(mpbpa)]2 (2), [MnBr2(mebpa)] (3) and [MnBr2(MeOH)(Hmepap)] (4) have been synthesized and characterized. Single-crystal Xray studies revealed that in all four complexes, the Mn(II) coordination spheres are distorted octahedral. In 1 and 2, the ether oxygen atom does not coordinate to the Mn(II) centre, but in 3 and 4 it does. The mononuclear molecules of 1 are linked by double hydrogen bonds to form linear chains. Temperature dependent magnetic susceptibility measurements revealed that the Mn(II) ions in 1 interact antiferromagnetically, with J=−1.06 cm−1. Compound 2 crystallizes as a double chloride-bridged dimer in which there is a weak ferromagnetic interaction (J=0.55 cm−1) between the Mn(II) pair. The solution EPR spectrum of 2 suggests that in methanol compound 2 decomposes to a great extent to mononuclear species. In compound 3, mebpa acts as a tetradentate ligand with all of its nitrogen and oxygen atoms coordinated to the Mn(II) ion. Unexpectedly, in complex 4, the phenolic oxygen of Hmepap remains protonated and does not coordinate to the metal ion. Instead the oxygen from a methanol molecule coordinates the manganese centre. Hydrogen bonds between one of the two bromide ions, and the methanol and phenol hydroxyl groups, respectively, connect the mononuclear molecules of 4 into chains. No magnetic interactions were observed between the Mn(II) ions in 3 or 4. 相似文献
20.
《Cell cycle (Georgetown, Tex.)》2013,12(3):543-553
Polo-like kinase 1 (Plk1) is elementary for cell proliferation and its deregulation is involved in tumorigenesis. Plk1 has been established as one of the most attractive targets for molecular cancer therapy. In fact, multiple small molecule inhibitors targeting either the kinase domain or the Polo-box binding domain (PBD) of Plk1 have been identified and intensively investigated. Intriguingly, Plk1 depletion affects more cancer cells than normal cells. It is also reported that the cytotoxicity induced by Plk1 inhibition is elevated in cancer cells with defective p53. The data lead to the hypothesis that p53 might be a predictive marker for the response of Plk1 inhibition. In this study, we demonstrate that there is no obvious different cytotoxic response between cancer cells with and without functional p53, including the isogenic colon cancer cell lines HCT116p53(+/+) and HCT116p53(-/-), breast cancer cell line MCF7, lung cancer cell line A549 and cervical carcinoma cell line HeLa, after treatment with either siRNA against Plk1, the kinase domain inhibitors BI 2536 and BI 6727 or the PBD inhibitor Poloxin. We suggest that the p53 status is not a predictor for the response of Plk1 inhibition, at least not directly. Yet, the long-term outcomes of losing p53, such as genome instability, could be associated with the cytotoxicity of Plk1 inhibition. Further studies are required to investigate whether other circumstances of cancer cells, such as DNA replication/damage stress, mitotic stress, and metabolic stress, which make possibly the survival of cancer cells more dependent on Plk1 function, are responsible for the sensitivity of Plk1 inhibition. 相似文献