共查询到20条相似文献,搜索用时 15 毫秒
1.
William C. Stallings Jenny P. Glusker H. L. Carrell Maria Bogucka-Ledóchowska Andrzej Ledóchowski John J. Stezowski 《Journal of biomolecular structure & dynamics》2013,31(3):511-524
Abstract Ledakrin (nitracrine), C-283, is a 1-nitro-9-aminoacridine derivative that is used in Poland as an antitumor agent. In order to investigate the basis of the activity of this compound the structure of another analog, [9-(3-dimethyl-l-methylpropylimino)-l-nitro-9, 10-dihydroacridine], C-829, that has similar activity, was determined by X-ray crystallographic techniques and was compared with that of ledakrin, already reported in the literature. In both molecules the proximity of the 1-nitro to the substituted 9-aminoacridine group causes extensive distortions. These compounds are believed to act, after metabolic “activation”, by cross-linking DNA. Such cross-linking does not occur in the absence of the 1-nitro group or if the nitro group is moved to the 2-, 3- or 4-position. Computer-assisted model-building has been used to test possible intercalative models. It has shown that functional groups on C-829 or C-283 are, when the acridine portion of the molecule is intercalated as in a proflavine dinucleoside phosphate complex, in positions suitable for DNA cross-linking by activated 1-nitro- 9-aminoacridine derivatives. 相似文献
2.
Jan M. Woynarowski Agnieszka Bartoszek Jerzy Konopa 《Chemico-biological interactions》1984,49(3):311-328
Ledakrin and seven other antitumor and cytotoxic derivatives of 1-nitro-9-aminoacridine were shown to induce DNA-single strand breaks in HeLa S3 cells as found by alkaline sucrose gradient centrifugation. The induced DNA damage is of non-random character. Some of Ledakrin-induced DNA breaks are probably generated by endonucleolytic cleavage in the course of repair processes as indicated by experiments with Novobiocin, an antibiotic preventing the incision step of DNA repair. Other Ledakrin-induced DNA breaks observed on alkaline sucrose gradients may arise from alkali-labile sites in DNA. Most of such sites seem to be converted to breaks after brief exposure to alkali. The extent of DNA damage by 1-nitro-9-aminoacridines was found to be correlated with cytotoxic activities of these compounds against HeLa S3 cells. Furthermore, Ledakrin and other derivatives seem to induce DNA-repair synthesis in HeLa S3 cells as judged by the stimulation of hydroxyurea (HU)-resistant incorporation of [3H] thymidine into DNA. The agents studied differ in their concentrations required to produce a considerable stimulation of DNA repair, whereas the maximal level of this effect is similar for all the derivatives assayed. The former values are correlated with cytotoxic activites of these compounds and seem to reflect the overall extent of DNA damage by 1-nitro-9-aminoacridines. Stimulation of DNA-repair synthesis is gradually shut off during prolonged incubation of the cells with Ledakrin or during postincubation of the cells in a drug-free medium. Such postincubation results also in the gradual accumulation of DNA-single strand breaks as observed by alkaline sucrose centrifugation. Hence, HeLa S3 cells are incapable of efficiently removing DNA damage by 1-nitro-9-aminoacridines, though the drug's action activates temporarily some repair mechanisms.The reported results suggest that overall DNA damage may contribute to the cytotoxic effects of 1-nitro-9-aminoacridines besides previously found ability of these agents to form interstrand DNA cross-links. 相似文献
3.
Three-dimensional, single-crystal, X-ray diffraction methods were used to determine the structure of the calcium chloride complex of α-d-allopyranosyl α-d-allopyranoside. The crystal is monoclinic with cell dimensions: a = 16.262(5), b = 8.345(5), c = 8.298(5)Å, β = 98.428(5)Å, and z = 2. The space group is P21. The structure was solved by three-dimensional Patterson and Fourier methods, and was refined by least-squares techniques to give a conventional discrepancy factor of R = 0.026; 2435 diffractometer-read reflections were used. The cation was found to be in 9-fold co-ordination to O-1, O-2, O-3, O-2′, O-3′, and four water molecules. 相似文献
4.
The synthesis and molecular structure of pentacarbonyl(3-methyl-l-(pyridin-2-yl)-l,2,4-triazole-N4)tungsten(0) are described. Surprisingly the ligand is bound to the W(CO)5 moiety via the triazole N4 (N24) atom, and the pyridine to triazole link is between the pyridine C2 (Cl) atom and the N1 (N21) atom of the triazole ring. The compound crystallises in the space group C2/c with a=24.559(18), b=9.693(16), c=13.817(12) Å, β=108.48(12)° and Z=8. A full matrix least-squares refinement resulted in a final R=0.052 (Rw=0.065) for 3688 unique reflections. 相似文献
5.
The preparation and X-ray structure of [Ag(9-EtGH-N7)2]NO3·H2O(9-EtGH=neutral 9-ethylguanine) is reported. The compound crystallizes in the triclinic system, space group P
with a=7.063(6), b=7.153(3), c=11.306(10) Å, α=83.36(6), β=76.66(7), γ=81.44(6)°. The cation is centrosymmetric with Ag(I) coordinated via two N7 positions and Ag---N7 bond lengths of 2.11(1) Å. Applying 109Ag NMR spectroscopy, complex formation constants for both the 1:1 complex (log β1=0.6) and the title compound (log β2=1.6) in Me2SO have been determined. 相似文献
6.
The compound (HOCH2CH2S)
) (1) has been prepared by the reaction of antimony(III) isopropoxide and 2-mercaptoethanol in a 1:2 molar ratio. Reaction of 1 with MOCH3 (where M = Li, Na and K) yields bimetallic products of the type, M[(OCH2CH2S)
)]. All these derivatives have been characterized by elemental analysis, IR, NMR (1H and 13C) spectra and molar conductivity measurements. Crystals of 1 are triclinic, space group P
, with a = 6.449(2), b = 10.285(2), c = 13.494(1) Å, α = 78.08(1), β = 75.99(1), γ = 71.54(2)°, V = 815.48 Å3, Z = 4, Dcalc = 2.239 g cm−3, (Mo Kα) λ = 0.7107 Å, μ = 3.55 mm−1, F(000) = 528, T = 295 K, final R = 0.0189 for 2344 reflections. One of the two mercaptoethanol moieties in 1 forms a five-membered chelate ring with antimony, Sb(1)---O(11) = 2.023(2) Å and Sb(1)---S(11) = 2.434(1) Å, while the other is bonded through the S atom only, Sb(1)---S(12) = 2.434(1) Å. The angles between these primary bonds with a mean value of 90.2° suggest a basically pyramidal, or pseudo tetrahedral structure if the stereochemically active lone pair is included in the coordination sphere. Two molecules are linked by intermolecular hydrogen bridges. The presence of weak intermolecular secondary bonding, Sb(1)---O(12) = 2.567(3) Å, in the complex indicates that the overall coordination polyhedron is best described in terms of a distorted trigonal bipyramidal arrangement. 相似文献
7.
M. R. Truter 《Inorganica chimica acta》1985,110(3):215-223
Reaction between lanthanum nitrate hexahydrate and a macrobicyclic polyether in ethanol has yielded a product of overall stoichiometry 3:2. The ligand, 21R, 26S, 29R, 34S-21, 22, 23, 24, 25, 26, 29, 30, 31,32,33, 34-dodecahydro-1,4,7,14,17,20,28,35-octaoxa (23,29syn218,34syn) (7.7) orthocyclophane, L, provides 8 oxygen donor atoms. Crystals were obtained from MeOH/EtOH (50/50). Crystal structure determination on 9590 observations, R=0.059, has shown the triclinic unit cell, a = 26.562(6), b = 13.486(3), c = 12.154(3) Å, α=63.9(1), β = 100.0(1), γ = 102.0(1)° space group P
, V = 3806 Å to contain, as the asymmetric unit, two complex cations (La(NO3)2L)+ and one complex anion (La- (NO3)5MeOH)2−. The lanthanum is 11-coordinated in the anion and one of the cations, in which there is one bidentate and one monodentate nitrate anion and 12-coordinated in the other cation. For the monodentate nitrate La---O = 2.448(9) Å, all other nitrate ions are bidentate (La---O = 2.594(9)−2.743(10) Å). Most La---O bonds are shorter in the 11 than in the 12-coordinated cation. There are large differences in La---O bond lengths according to the nature of the carbon atoms to which the oxygen is attached. The methanol molecule forms a hydrogen bond to one oxygen atom of the monodentate nitrate group. 相似文献
8.
J Markovits D Wilmańska E Lescot K Studzian L Szmigiero M Gniazdowski 《Chemico-biological interactions》1989,70(1-2):73-87
Two 1-nitro-9-aminoacridine dimers were prepared: one bearing a spermine flexible linking chain, compound 4, the other a rigid dipiperidine-type linker, compound 7. Both dimers elicited a higher affinity constant for DNA than the parent monomeric drug nitracrine 2. This affinity was several orders lower than what was found for other dimeric compounds having the same linkers and no nitro group on the acridine ring (3, 5, 6 and 8). Bisintercalation was evidenced for compound 4 by viscosimetric measurements. In the absence of dithiothreitol, an inhibitory effect of RNA synthesis in vitro was observed for all the tested compounds except 2 and 7. In the presence of dithiothreitol, 4 and 7 formed irreversible complexes with DNA of decreased template properties. The level of the dimers binding was lower than that of the parent compound 2. Cross-links were detected by means of hydroxylapatite chromatography in a complex of the dimer bearing a flexible linking chain, compound 4 with DNA, while the compound 7-DNA complex eluted in the single-stranded DNA region. The extent of cytotoxicity of the two 1-nitro-9-aminoacridine dimers against L1210 cultured cells was different. 相似文献
9.
The enzyme 1-aminocyclopropane-1-carboxylic acid deaminase from the bacterium Pseudomonas sp. has been crystallized using the hanging-drop method. The crystals belong to the orthorhombic space group P 212121 (a = 70.0 Å, b = 70.0 Å, c = 355.0 Å). An asymmetrical unit contains two trimer molecules of Mr = 110,000. The diffraction data have been collected to 3.5-Å resolution. Analysis of the data using the self-rotation function suggests threefold axes within the trimer molecules and a pseudotetragonal arrangement between the trimer molecules in the cell. 相似文献
10.
Bis(pentamethylcyclopentadienyl)samarium bis- (tetrahydrofuranate), (C5Me5)2Sm(THF)2, reacts with 2,3,5,6-tetramethylphenol in toluene to yield (C5Me5)2Sm(OC6HMe4-2,3,5,6). The compound crystallizes in the space group P21/c with a = 8.725(3) Å, b=18.821(6) Å, c=18.461(6) Å, β= 111.17(2)°, V = 2827(2) Å3 and Dc=1.340 g cm−3 for Z = 4. Molecules of the aryloxide complex are monomeric and exhibit a bent metallocene structure with a nearly linear Sm---O---C(aryloxide) linkage: Sm---O = 2.13(1) Å, O---C = 1.29(2) Å, and Sm---O---C = 172.3(13)°. Reaction of the samarium complex with phenyllithium produces the previously- characterized species (C5Me5)2Sm(C6H5)(THF). 相似文献
11.
George T. DeTitta James W. Edmonds William L. Duax 《Prostaglandins & other lipid mediators》1975,9(5):659-665
The molecular conformation of the monoclinic crystalline polymorph of prostaglandin A1 has been determined by X-ray diffraction techniques. The space group is P21 with a = 13.637 (2), b = 7.567 (1), I c = 10.576 (2) Å, β = 107.37 (3)°; Dc = 1.073 g·cm−3 for Z = 2. The molecular conformation is characterized by the nearly parallel arrangement of the C1–C7 and C13–C20 side chains, with a general flattening of the overall structure when compared with the orthorhombic polymorph. The cyclopentenone moiety assumes a C8 envelope conformation with C8 and O9 displaced +0.29 Å and −0.18 Å from the C9–C10=C11–C12 plane respectively. Concerted, small variations of the torsion angles, primarily about the C8–C12, C14–C15 and C16–C17 bonds, bring the monoclinic and orthorhombic conformations into coincidence. 相似文献
12.
Substituted 1-nitro-9-aminoacridine derivatives were shown to inhibit RNA and to a lesser extent protein synthesis in cultured human cells. Complex formation between the compounds studied and DNA were considered to be responsible for their cytostatic action. Two types of complexes differing in their binding forces were found. The biological activity of the studied compounds seems not to be dependent on the existence of a positive charge on the acridine ring. 相似文献
13.
J Michalska 《Mutation research》1986,170(3):119-123
The induction of chromosomal aberrations by 5 derivatives of nitro-9-aminoacridine in V79 Chinese hamster cells was observed. The clastogenic activity of the compounds tested depended on the position of the NO2 group in the acridine ring. The strongest clastogens were derivatives with NO2 in position 1. The remaining derivatives placed in decreasing order of clastogenic activity were: 3-nitro, 4-nitro and 2-nitro. In addition, 2-nitro and 3-nitro derivatives produced hyperdiploid/polyploid metaphases. 相似文献
14.
Bernd Johannsen Bernhard Noll Peter Leibnitz Günter Reck Steffi Noll Hartmut Spies 《Inorganica chimica acta》1993,210(2)
The reaction of mercaptoacetyl diglycine (MAG2) with technetium(V) gluconate in aqueous solution produced [TcO(MAG2)]−. A single X-ray structure determination was carried out for the tetraphenylarsonium salt. The dark brown crystals are monoclinic, space group P2(1)/n, with a=12.478(5), b=14.922(5), c=17.183(9) Å and Z=4. The [TcO(MAG2)]− ion has a square pyramidal geometry with the technetium atom displaced by 0.756 Å towards the oxo ligand from the plane formed by the equatorial S,N,N,O atoms. The rhenium complex AsPh4[ReO(MAG2)] was prepared analogously starting from Re(V) gluconate and characterized. 相似文献
15.
Shigehiro Kamitori Tomoya Satou Takashi Tonozuka Yoshiyuki Sakano Hiroshi Matsuzawa Kenji Okuyama 《Journal of structural biology》1995,114(3)
Crystals of Thermoactinomyces vulgaris α-amylase II, which is a new type of α-amylase having hydrolysis activities for pullulan and cyclodextrins, have been obtained and diffraction data to 2.9 Å resolution were collected. The crystal belongs to an orthorhombic system with cell dimensions of a = 119.5 Å, b = 120.6 Å, and c = 114.6 Å and a space group of P 212121. Two or three protein molecules are expected to exist in an asymmetric unit. 相似文献
16.
To define a critical lesion in presumable target DNA cause in vivo by the antitumor and cytotoxic 1-nitroacridines, Ehrlich ascites tumor (Eat) cells implanted into mice, HeLa cells grown in monolayer culture or Bacillus subtilis SB 1058 strain cells were exposed to Ledakrin [Nitracrine; 1-nitro-9-(3'-dimethylamino-n-propylamino)acridine], its non-antitumor congeners, or mitomycin C tested for comparison; total intracellular DNA was isolated from control or treated cells and denatured by heat, alkali or formamide, after which the chemically-induced fraction of interstrand cross-linked DNA molecules was assessed by thermal denaturation-renaturation curve analysis, hydroxylapatite column chromatography, or partitioning in a Dextran T500-polyethylene glycol 6000 biphasic system. Ledakrin, as compared to mitomycin C, was a very effective cross-linking agent, inducing one covalent cross-link per approx. 20 X 10(3) (B. subtilis), 56 X 10(3) (HeLa) or 80 X 10(3) (Eat) DNA base pairs. The first cross-links were introduced in B. subtilis cell genomes at minimal bactericidal concentrations of Ledakrin of mitomycin C. Ledakrin failed to induce discernible cross-linking of bihelical DNA when complexed with in cell-free system. Unlike the other two 1-nitroacridines which cross-linked DNA of cultured HeLa or B. subtilis cells, the non-antitumor 2-, 3- or 4-nitroacridines did not cause such effect and diminished cross-linking by Ledakrin or mitomycin C. Hence, upon metabolic activation in mammalian or bacterial cell Ledakrin and, most probably other 1-nitroacridines, become very effective DNA cross-linking agents and such effects appear to be responsible for the antitumor and potent cytotoxic activities of 1-nitroacridines. 相似文献
17.
The reactive palladium dimer, [Pd(dppm)(O2CCF3)]2, is carbonylated to [Pd(dppm)(O2CCF3)]2(μ-CO) in a reversible reaction with K = c. 7.2(2)x104 atm−1 (P1/2 = c. 2.4 Torr). This is significantly larger than is expected based on the λmax = 280 nm in the electronic spectrum. The product can be isolated in analytically pure form by crystallization under a CO atmosphere. It forms crystals in the monoclinic space group Cc with a = 18.584(5), b = 28.65(1), c = 11.164(3) Å and β = 95.16(2)°. The structure is significantly distorted. The bonding about the two palladium atoms is quite asymmetric. While one is close to a square planar geometry with a Pd---C(O) distance of 1.90(2) Å, the other is significantly pyramidalized and has a longer (2.00(2) Å) bond to the bridging CO. The Pd---Pd distance is only 2.896(2) Å, much shorter than that usually observed for formally non-bonded Pd atoms. 相似文献
18.
Structural analysis of 6-S-(benzoxazol-2-yl)-6-deoxy
Miles T. Lakin Nadine Mouhous-Riou Christelle Lorin Patrick Rollin Jan Kroon Serge Prez 《Carbohydrate research》1996,290(2)
The conformational behaviour of a representative azaheterocycle/thiosugar hybrid:
, 1, has been characterised by X-ray crystallography, molecular modelling and NMR studies. The crystal of 1 (C19H23NO6S) belongs to the monoclinic space group P21, with α = 8.4330(4), B = 10.287(3), C = 11.417(4) Å, β = 101.66(5)°, V = 970.0(5) Å3, and Z = 2. The structure has been determined by X-ray diffraction at 299 K using an area detector. Least-squares refinement based on 2352 reflections yielded a final wR2 of 0.098, with R1 = 0.040 [for 2210 reflections with Fo > 4σ(Fo)]. The pyranose ring adopts a conformation between that of the screw-boat, OS5, and the twist-boat, OT2 forms. Proton NMR chemical shifts have been assigned by measurement of ID and 2D spectra. The C-5-C-6 conformer populations in CDC13 solution have been estimated. In parallel, a 相似文献
Full-size image
19.
20.
E. Licandro S. Maiorana A. Papagni A. Zanotti GerosaF. Cariati S. BruniM. MoretA. Chiesi Villa 《Inorganica chimica acta》1994,220(1-2)
Cycloaddition reactions with α,β-unsaturated carbene complexes of the Fischer-type bearing the carbene carbon atom and the double bond incorporated in the same ring are described. Pentacarbonyl(2H-benzopyran-2- ylidene)chromium(0) complexes (2a-c) and pentacarbonyl(4-methoxy-3,3-dimethyl-2-oxacyclopentylidene)- chromium(0) (3) show a rather low reactivity towards 1,3-dipoles and 1,3-dienes. The reactions with diazomethane are regioselective but not chemoselective; compounds 2 and 3 show two sites of attack: the α,β carbon-carbon and the carbon-metal double bond. The crystal and molecular structures of 2a and 3 have been elucidated by single crystal X-ray analysis. Crystals of 2a are monoclinic, space group P21/c, a=7.614(3), b=14.033(3), c=12.766(3) Å, β=95.24°, V=1358.3(7) Å Z=4; crystals of 3 are triclinic, space group P
, a=6.553(1), b=9.408(1), c=10.620(1) Å α=92.70(1), β=92.30(1), γ=92.12(1)°, V=653.0(1), Å3, Z=2. Final agreement indices for 2a and 3 are R=0.034 and 0.033, respectively. Vibrational properties of the Cr(CO)5 moiety were interpreted by FT-IR and FT-Raman spectroscopy. Electronic spectra and π electron distribution were interpreted by resonance Raman spectroscopy. 相似文献