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1.
Hall MD Alderden RA Zhang M Beale PJ Cai Z Lai B Stampfl AP Hambley TW 《Journal of structural biology》2006,155(1):38-44
SRIXE mapping has been used to gain insight into the fate of platinum(II) and platinum(IV) complexes in cells and tumours treated with anticancer active complexes to facilitate the development of improved drugs. SRIXE maps were collected of thin sections of human ovarian (A2780) cancer cells treated with bromine containing platinum complexes, cis-[PtCl(2)(3-Brpyr)(NH(3))] (3-Brpyr=3-bromopyridine) and cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] (OAcBr=bromoacetate), or a platinum complex with an intercalator attached cis-[PtCl(2)(2-[(3-aminopropyl)amino]-9,10-anthracenedione)(NH(3))]. After 24h the complexes appear to be localised in the cell nucleus with a lower concentration in the surrounding cytoplasm. In cells treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] the concentration of bromine was substantially higher than in control cells and the bromine was co-localised with the platinum consistent with the 3-bromopyridine ligand remaining bound to the platinum. The cells treated with cis,trans,cis-[PtCl(2)(OAcBr)(2)(NH(3))(2)] also showed an increased level of bromine, but to a much lesser extent than for those treated with cis-[PtCl(2)(3-Brpyr)(NH(3))] suggestive of substantial reduction of the platinum(IV) complex. Maps were also collected from thin sections of a 4T1.2 neo 1 mammary tumour xenograft removed from a mouse 3h after treatment with cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)] and revealed selective uptake of platinum by one cell. 相似文献
2.
Hall MD Amjadi S Zhang M Beale PJ Hambley TW 《Journal of inorganic biochemistry》2004,98(10):1614-1624
The reduction potentials, lipophilicities, cellular uptake and cytotoxicity have been examined for two series of platinum(IV) complexes that yield common platinum(II) complexes on reduction: cis-[PtCl(4)(NH(3))(2)], cis,trans,cis-[PtCl(2)(OAc)(2)(NH(3))(2)], cis,trans,cis-[PtCl(2)(OH)(2)(NH(3))(2)], [PtCl(4)(en)], cis,trans-[PtCl(2)(OAc)(2)(en)] and cis,trans-[PtCl(2)(OH)(2)(en)] (en=ethane-1,2-diamine, OAc=acetate). As previously reported, the reduction occurs most readily when the axial ligand is chloride and least readily when it is hydroxide. The en series of complexes are marginally more lipophilic than their ammine analogues. The presence of axial chloride or acetate ligands results in a slighter higher lipophilicity compared with the platinum(II) analogue whereas hydroxide ligands lead to a substantially lower lipophilicity. The cellular uptake is similar for the platinum(II) species and their analogous tetrachloro complexes, but is substantially lower for the acetato and hydroxo complexes, resulting in a correlation with the reduction potential. The activities are also correlated with the reduction potentials with the tetrachloro complexes being the most active of the platinum(IV) series and the hydroxo being the least active. These results are interpreted in terms of reduction, followed by aquation reducing the amount of efflux from the cells resulting in an increase in net uptake. 相似文献
3.
The cellular pharmacology of two pairs of cis and trans platinum complexes has been studied in three human ovarian carcinoma cell lines, a parental relatively cisplatin-sensitive line (CH1), a subline possessing acquired cisplatin resistance (3-fold; CH1cisR) and an intrinsically cisplatin resistant line (13-fold; SKOV-3). Growth inhibition studies showed that both JM335 [trans ammine (cyclohexylaminedichloro dihydroxo) platinum(IV)] and its platinum(II) dichloro homolog JM334 were relatively less cross-resistant against both acquired and intrinsic cisplatin resistant cells. In contrast, resistance circumvention was not apparent in these cell lines with their cis isomeric counterparts (JM149 for JM335 and JM118 for JM334). The trans compound JM335 was more potent than its cis isomer against all three cell lines. There was no clear correlation between intracellular accumulation following 2 h exposure to each compound and resulting DNA platination or growth inhibition. The selective activity of the trans platinum complexes against the SKOV-3 cell line correlated with a deficiency in the repair of adducts within a fragment of the N-ras gene induced by trans compounds whereas adducts induced by the cis counterparts, and cisplatin, were repaired. The CH 1 parental line appeared repair deficient at the gene-specific level to adducts induced by both cis (including cisplatin) and trans compounds. Resistance in CH1cisR was associated with a lack of gene-specific repair of lesions formed by JM118 and JM149. All four compounds induced apoptosis in all three cell lines, as measured by fluorescent microscopy and field inverted gel electrophoresis, although the kinetics of apoptosis was markedly faster for the trans versus cis compounds. In summary, the trans platinum complexes JM335 and JM334 possess unique cellular properties compared to their cis counterparts particularly with respect to gene specific repair of DNA adducts and the rate of induction of apoptosis. 相似文献
4.
A unique multibranched cyclomaltooligosaccharide (cyclodextrin, CD) of 6(1),6(3),6(5)-tri-O-alpha-maltosyl-cyclomaltoheptaose [6(1),6(3),6(5)-tri-O-alpha-maltosyl-beta-cyclodextrin, (G(2))(3)-betaCD] was prepared. The physicochemical and biological properties of (G(2))(3)-betaCD were determined together with those of monobranched CDs (6-O-alpha-D-glucopyranosyl-alpha-cyclodextrin (G(1)-alphaCD), 6-O-alpha-D-glucopyranosyl-beta-cyclodextrin (G(1)-betaCD), and 6-O-alpha-maltosyl-beta-cyclodextrin (G(2)-betaCD)). NMR spectra of (G(2))(3)-betaCD were measured using various 2D NMR techniques. The solubility of (G(2))(3)-betaCD in water and MeOH-water solutions was extremely high in comparison with nonbranched betaCD and was about the same as that of the other monobranched betaCDs. The formation of an inclusion complex of (G(2))(3)-betaCD with stereoisomers (estradiol, retinoic acid, quinine, citral, and glycyrrhetinic acid) depends on the cis-trans isomers of guest compounds. The cis isomers of estradiol, retinoic acid, and glycyrrhetinic acid were included more than their trans isomers, while the trans isomers of citral and quinine fit more tightly than their cis isomers. (G(2))(3)-betaCD was the most effective host compound in the cis-trans resolution of glycyrrhetinic acid. Among the branched betaCDs, (G(2))(3)-betaCD exhibited the weakest hemolytic activity in human erythrocytes and showed negligible cytotoxicity in Caco-2 cells up to 200 microM. These results indicate unique characteristics of (G(2))(3)-betaCD in some biological responses of cultured cells. 相似文献
5.
Polynuclear platinum compounds comprise a unique class of anticancer agents with chemical and biological properties different from mononuclear platinum drugs. The lead compound of this class is bifunctional trinuclear platinum complex [[trans-PtCl(NH(3))(2)](2)mu-trans-Pt(NH(3))(2)[H(2)N(CH(2))(6)NH(2)](2)](4+) (1,0,1/t,t,t, BBR 3464). Interestingly, the geometry of the coordination spheres in this compound affects potency. For example, the central cis unit of [[trans-PtCl(NH(3))(2)](2)mu-cis-Pt(NH(3))(2)[H(2)N(CH(2))(6)NH(2)](2)](4+) (1,0,1/t,c,t, BBR 3499) results in substantially reduced cytotoxicity. It has been shown that the interactions of polynuclear platinum drugs with target DNA are distinct from the mononuclear-based cisplatin family. In the present work the DNA binding of 1,0,1/t,c,t in cell-free media was examined by the methods of molecular biophysics and compared to the binding of 1,0,1/t,t,t. The binding of 1,0,1/t,c,t is slower and less sequence specific. 1,0,1/t,c,t also forms on DNA long-range delocalized intrastrand and interstrand cross-links similarly as 1,0,1/t,t,t, although the frequency of interstrand adducts is markedly enhanced. Importantly, the adducts of 1,0,1/t,c,t distort DNA conformation and are repaired by cell-free extracts considerably more than the adducts of 1,0,1/t,t,t. It has been suggested that the unique properties of long-range interstrand cross-links of bifunctional trinuclear platinum complexes and resulting conformational alterations in DNA have critical consequences for their antitumor effects. 相似文献
6.
L A Eslava J B Putnam L Pedersen 《International journal of peptide and protein research》1978,11(2):149-153
ab initio Calculations at the Gaussian-70 STO-3G and 4-31G basis levels have been carried out for (HS)2 and (CH3S)2. Cystine was investigated at the STO-3G level. The STO-3G energy minimized geometry agrees well with experiments for (HS)2 and (CH3S)2. The barriers to internal rotation are predicted to be (at the 4.31G level): (HS)2, cis 8.5 kcal, trans 3.03 kcal; (CH3S)2, cis 18.47 kcal, trans 6.04 kcal. 相似文献
7.
Several cisplatin analogues of ethylenediamine-derived ligands containing alcohol, carboxylic acid and acetate substituents have been prepared and characterised. Oxidation of some of these square planar platinum(II) complexes using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes, containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved by reaction with acetic anhydride, giving complexes which are analogues of the antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl2], where H2L4 is ethylenediamine-N,N'-diacetic acid, with H2O2 gave the platinum(IV) complex [PtL4Cl2].H2O in which L4 is tetradentate as shown by a crystal and molecular structure. This complex was previously reported to be [Pt(HL4)(OH)Cl2] in which HL4 is tridentate. Several of the complexes were tested for antitumour activity against five human ovarian carcinoma cell lines. IC50 values range from 4.0 microM for cis,trans-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to >25 microM indicating moderate to low activity relative to other platinum complexes. 相似文献
8.
Self-assembled ternary complex of cationic dendrimer,cucurbituril, and DNA: noncovalent strategy in developing a gene delivery carrier 总被引:5,自引:0,他引:5
A ternary complex of PPI-DAB dendrimer [(1,4-diaminobutane); Gen = N; dendri-poly(propyleneimine); -[NHC(=O)CH(2)NH(2)(+)(CH(2))(4)NH(3)(+)](z)()], DNA, and cucurbituril (CB) was evaluated as an example of a totally self-assembled gene delivery carrier. The complex was formed in a noncovalent way in which DNA interacts with PPI-DAB electrostatistically and CB with PPI-DAB through multiple noncovalent interactions. Dynamic light scattering data indicated that the diameter and size distributions of the complexes were dependent upon the sequence of mixing of each component with unimodal distribution ranging from 150.8 to 210.2 nm under favorable conditions. Fluorescence studies showed the quantitative binding of CB to PPI-DAB after ternary complex formation. The complex was able to transfect mammalian cells with high efficiency and the cytotoxicity of the PPI-DAB/CB complex was relatively low. 相似文献
9.
Patel RN Singh N Shukla KK Gundla VL Chauhan UK 《Journal of inorganic biochemistry》2005,99(2):651-663
Four imidazolate-bridged binuclear copper(II)-copper(II) and copper(II)-zinc(II) complexes viz., [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH, [(Phen)(2)Cu-Im-Cu(Phen)(2)](BF(4))(3).2CH(3)OH, [(Bipy)(2)Cu-Im-Zn(Bipy)(2)](BF(4))(3), and [(Phen)(2)Cu-Im-Zn(Phen)(2)](BF(4))(3), (Bipy=2,2'-Bipyridyl, Phen=1-10-Phenanthroline and Im=imidazolate ion) were synthesized as a possible models for superoxide dismutase (SOD). Complex [(Bipy)(2)Cu-Im-Cu(Bipy)(2)](ClO(4))(3).CH(3)OH has been structurally characterized. This complex crystallizes in the triclinic space group P1, with the unit parameters a=8.88(5) A, b=13.79(17) A, c=20.18(18) A, alpha=76.424(8)(o), beta=85.888(6)(o), gamma=82.213(7). The metal-nitrogen bond length from 1.972-2.273 A and the distance Cu-Cu is 5.92 A. The five-coordinate geometry about the copper(II) ion is square pyramidal. Magnetic moment and electron paramagnetic resonance (e.p.r.) spectral measurements of the homobinuclear complexes have shown an antiferromagnetic exchange interaction. From the e.p.r. and UV-Vis spectral measurement studies, these complexes have been found to be stable (pH 8.5-10.5 for 1, 10.5 for 2,3 and 8.5 for 4). These complexes catalyse the dismutation of superoxide radical (O(2)(-)) at biological pH. All the observations indicate that these complexes act as good possible models for superoxide dismutase. 相似文献
10.
Paschke R Kalbitz J Paetz C Luckner M Mueller T Schmoll HJ Mueller H Sorkau E Sinn E 《Journal of inorganic biochemistry》2003,94(4):335-342
This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue. 相似文献
11.
Terrón A García-Raso A Fiol JJ Amengual S Barceló-Oliver M Tótaro RM Apella MC Molins E Mata I 《Journal of inorganic biochemistry》2004,98(4):632-638
Four new complexes of uracilato and 5-halouracilato with the divalent metal ions Cu(II), Zn(II) and Ni(II) were obtained and structurally characterized. [Cu(uracilato- N(1))(2)(NH(3))(2)].2(H(2)O) (1) and [Cu(5-chlorouracilato-N(1))(2)(NH(3))(2)](H(2)O)(2) (2) complexes present distorted square planar co-ordination geometry around the metal ion. Although an additional axial water molecule is present [Cu(II)-OH(2)=2.89 A (for 1) and 2.52 A (for 2)] in both cases, only in the complex 2 would be considered in the limit of a bond distance. The Zn(II) in [Zn(5-chlorouracilato-N(1))(NH(3))(3)].(5-chlorouracilato-N(1)).(H(2)O) presents a tetrahedral co-ordination with three ammonia molecules and the N(1) of the corresponding uracilato moiety. A non-coordinated uracilato molecule is present as a counterion and a recognition between co-ordinated and free ligands, by means a tandem of H-bonds, should be mentioned. Finally, the complex [Ni(5-chlorouracilato-N(1))(2)(en)(2)] (H(2)O)(2) (where en is ethylenediamine) presents a typical octahedral trans co-ordination with additional hydrogen bonds between 5-chlorouracilato and the NH(2) groups of ethylenediamine units. 相似文献
12.
Two metal complexes formulated as [Zn(L)(2)](2)·H(2)O (1) and [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)-phenylthiosemicarbazone, have been synthesized and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological studies, carried out in vitro against selected bacteria and the K562 leukemia cell lines, respectively, have shown that the free ligand and its two complexes may be endowed with important biological properties, especially HL with MIC=3.90 μg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 μM against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert their cytotoxicity activity via induced loss of mitochondria membrane potential (MMP). 相似文献
13.
Egger A Cebrián-Losantos B Stepanenko IN Krokhin AA Eichinger R Jakupec MA Arion VB Keppler BK 《化学与生物多样性》2008,5(8):1588-1593
The antiproliferative properties of the osmium(II) complexes cis,fac-[Os(II)Cl(2)(DMSO)(3)(L)] and trans,cis,cis-[Os(II)Cl(2)(DMSO)(2)(L)(2)] (L = 1H-pyrazole, 1H-imidazole) were studied in three human cancer cell lines, namely 41M (ovary), SK-BR-3 (breast), and SW480 (colon). Their activities were compared with those of osmium(III) and ruthenium(III) NAMI-A type complexes on HT-29 (colon) and SK-BR-3 cancer cell lines. While IC(50) values of all the Os(II) complexes were found to be >1000 microM in all cell lines, Os and Ru-NAMI-A type complexes showed remarkable antiproliferative activity. The marginal in vitro cytotoxicity of the Os(II) compounds is presumably attributed to their resistance to hydrolysis. However, the Os-NAMI-A complexes, which are also kinetically stable in aqueous solution, showed reasonable antiproliferative activity in vitro when compared with the analogous Ru compounds and with the Os(II)-DMSO-azole species, indicating that hydrolysis might be not a prerequisite for the antitumor activity of Os-NAMI-A type complexes. 相似文献
14.
Diiron model complexes (micro-SCH(2)CH(2)CH(2)S)Fe(2)(CO)(5)L with thioether-substitution, L=S(CH(2)CH(3))(2) (2), S(CH(2)CH(3))(CH(2)CH(2)Cl) (3), S(CH(2)CH(3))(C(6)H(5)) (4), or sulfoxide-substitution, L=SO(CH(2)CH(2)CH(3))(2) (5), SO(CH(3))(2) (6), were synthesized as active site analogues of Fe-only hydrogenase. The organosulfur ligands were introduced into the diiron centers via moderately stable intermediates following two routes. The X-ray crystallographic structures of complexes 2-6 show the apical positions of terminal organosulfur ligands. The electrochemical behaviors of the model complexes were investigated, especially for the interesting properties of the derivative of 6 which is proposed to be the first model with weak donor ligand similar to CO. 相似文献
15.
Tsoukalas C Pirmettis I Patsis G Pelecanou M Bodo K Raptopoulou CP Terzis A Papadopoulos M Chiotellis E 《Journal of inorganic biochemistry》2003,93(3-4):213-220
The [NS][S](2) mixed-ligand system was applied to synthesize oxorhenium and oxotechnetium complexes of the general formula MO(o-CH(3)OC(6)H(4)N(CH(2)CH(2))(2)NCH(2)CH(2)S)(p-CH(3)C(6)H(4)S)(2) (M=Re in 1, M=(99)Tc in 2, and M=(99m)Tc in 3). The bidentate [NS] ligand includes the 1-(2-methoxyphenyl)piperazine moiety which is a fragment of the true 5-HT(1A) antagonist WAY 100635. The oxorhenium complex 1 was prepared by a ligand exchange reaction using ReOCl(3)(PPh(3))(2) as precursor while [Bu(4)N][(99)TcOCl(4)] and (99)Tc-gluconate were used as precursors in the synthesis of the oxotechnetium-99 complex 2. Both complexes were characterized by elemental analysis and spectroscopic methods. Crystallographic analysis of 1 showed that the rhenium coordination geometry is trigonal bipyramidal. The basal plane of the trigonal bipyramid is defined by the oxo group and two sulphur atoms, one belonging to the [NS] ligand and the other to an aromatic thiol, while the apical positions are occupied by the nitrogen of the [NS] ligand and the sulphur of the second aromatic thiol. The oxotechnetium-99 complex 2 has almost identical unit cell parameters to those of the oxorhenium complex 1 indicating, in combination with the other analytical data, that the complexes are isostructural. The binding affinity of the oxorhenium complex 1 for the 5-HT(1A) receptor subtype was determined in rat brain hippocampal preparations (IC(50)=106 nM). The oxotechnetium-99m complex 3 was prepared by a ligand exchange reaction using (99m)Tc-glucoheptonate as the precursor. Its structure was established by comparative HPLC studies using the oxotechnetium-99 complex 2 as a reference. Complex 3 was administered by intravenous injection in rats. At 2 min post injection, 0.153% of the injected dose per gram of tissue was measured in rat brain. 相似文献
16.
Ramachandran E Kalaivani P Prabhakaran R Rath NP Brinda S Poornima P Padma VV Natarajan K 《Metallomics : integrated biometal science》2012,4(2):218-227
New complexes, [Ni(HL)(PPh(3))]Cl (1), [Pd(L)(PPh(3))](2), and [Pd(L)(AsPh(3))](3), were synthesized from the reactions of 4-chloro-5-methyl-salicylaldehyde thiosemicarbazone [H(2)L] with [NiCl(2)(PPh(3))(2)], [PdCl(2)(PPh(3))(2)] and [PdCl(2)(AsPh(3))(2)]. They were characterized by IR, electronic, (1)H-NMR spectral data. Further, the structures of the complexes have been determined by single crystal X-ray diffraction. While the thiosemicarbazone coordinated as binegative tridentate (ONS) in complexes 2 and 3, it is coordinated as mono negative tridentate (ONS) in 1. The interactions of the new complexes with calf thymus DNA was examined by absorption and emission spectra, and viscosity measurements. Moreover, the antioxidant properties of the new complexes have also been tested against DPPH radical in which complex 1 exhibited better activity than that of the other two complexes 2 and 3. The in vitro cytotoxicity of complexes 1-3 against A549 and HepG2 cell lines was assayed, and the new complexes exhibited higher cytotoxic activity with lower IC(50) values indicating their efficiency in killing the cancer cells even at very low concentrations. 相似文献
17.
18.
Anna C. G. Hotze Sabrine E. Caspers Dick de Vos Huub Kooijman Anthony L. Spek Anna Flamigni Marina Bacac Gianni Sava Jaap G. Haasnoot Jan Reedijk 《Journal of biological inorganic chemistry》2004,9(3):354-364
The dichlorobis(2-phenylazopyridine)ruthenium(II) complexes, [Ru(azpy)(2)Cl(2)], are under renewed investigation due to their potential anticancer activity. The three most common isomers alpha-, beta- and gamma-[RuL(2)Cl(2)] with L= o-tolylazopyridine (tazpy) and 4-methyl-2-phenylazopyridine (mazpy) (alpha indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, trans, cis positions, beta indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual cis, cis, cis positions, and gamma indicating the coordinating Cl, N(pyridine) and Nazo atoms in mutual trans, cis, cis positions) are synthesized and characterized by NMR spectroscopy. The molecular structures of gamma-[Ru(tazpy)(2)Cl(2)] and alpha-[Ru(mazpy)(2)Cl(2)] are determined by X-ray diffraction analysis. The IC(50) values of the geometrically isomeric [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] complexes compared with those of the parent [Ru(azpy)(2)Cl(2)] complexes are determined in a series of human tumour cell lines (MCF-7, EVSA-T, WIDR, IGROV, M19, A498 and H266). These data unambiguously show for all complexes the following trend: the alpha isomer shows a very high cytotoxicity, whereas the beta isomer is a factor 10 less cytotoxic. The gamma isomers of [Ru(tazpy)(2)Cl(2)] and [Ru(mazpy)(2)Cl(2)] display a very high cytotoxicity comparable to that of the gamma isomer of the parent compound [Ru(azpy)(2)Cl(2)] and to that of the alpha isomer. These biological data are of the utmost importance for a better understanding of the structure-activity relationships for the isomeric [RuL(2)Cl(2)] complexes. 相似文献
19.
Effect of the Thiol-Oxidizing Agent Diamide on the Growth of Escherichia coli 总被引:4,自引:2,他引:2
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Richard Wax Eugene Rosenberg Nechama S. Kosower Edward M. Kosower 《Journal of bacteriology》1970,101(3):1092-1093
Oxidation of glutathione within Escherichia coli cells by diamide, (CH(3))(2)NCON=NCON(CH(3))(2), stops growth but does not cause cell death. Normal growth rates are resumed after periods which vary in length according to the diamide concentration. Consumption of excess reagent with added glutathione quickly reverses the inhibition. Another thiol-oxidizing agent, azoester, C(6)H(5)N=NCOOCH(3), causes lysis. 相似文献
20.
Permyakov SE Knyazeva EL Khasanova LM Fadeev RS Zhadan AP Roche-Hakansson H Håkansson AP Akatov VS Permyakov EA 《Biological chemistry》2012,393(1-2):85-92
HAMLET is a complex of α-lactalbumin (α-LA) with oleic acid (OA) that selectively kills tumor cells and Streptococcus pneumoniae. To assess the contribution of the proteinaceous component to cytotoxicity of HAMLET, OA complexes with proteins structurally and functionally distinct from α-LA were prepared. Similar to HAMLET, the OA complexes with bovine β-lactoglobulin (bLG) and pike parvalbumin (pPA) (bLG-OA-45 and pPA-OA-45, respectively) induced S. pneumoniae D39 cell death. The activation mechanisms of S. pneumoniae death for these complexes were analogous to those for HAMLET, and the cytotoxicity of the complexes increased with OA content in the preparations. The half-maximal inhibitory concentration for HEp-2 cells linearly decreased with rise in OA content in the preparations, and OA concentration in the preparations causing HEp-2 cell death was close to the cytotoxicity of OA alone. Hence, the cytotoxic action of these complexes against HEp-2 cells is induced mostly by OA. Thermal stabilization of bLG upon association with OA implies that cytotoxicity of bLG-OA-45 complex cannot be ascribed to molten globule-like conformation of the protein component. Overall, the proteinaceous component of HAMLET-like complexes studied is not a prerequisite for their activity; the cytotoxicity of these complexes is mostly due to the action of OA. 相似文献