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1.
《Mutation Research Letters》1994,323(1-2):75-79
DNA strand breaks, measured by alkaline elution, and hypoxanthine guanine phosphoribosyltransferase (HPRT) mutation were studied in V79 cells after photochemical treatment (PCT) or exposure to X-rays. Cells were incubated with the photosensitizers Photofrin II (PII) and three closely related porphyrins tetra-(3-hydroxyphenyl) porphyrin (3THPP), meso-tetra-(4-sulfonatophenyl) porphine (TPPS4) and meso-tetra-(N-methyl-4-pyridyl) porphine (TMPyPH2). These dyes are assumed to act on cellular targets mainly via singlet oxygen when excited by light. While the hydrophilic TPPS4 and TMPyPH2 did not photoinduce mutants to any significant extent, both lipophilic dyes, 3THPP and PII, were significantly mutagenic when excited by light. On the other hand, TPPS4 was the most efficient sensitizer of alkali-labile DNA strand breaks, while TMPyPH2 did not induce any significant amount of either type of DNA damage. Surprisingly, no correlation between the two parameters was found for PCT, either after exposures inactivating 50% of the cells or after exposures inactivating 90% of them. The lack of correlation between the yields of DNA strand breaks and of mutants could not be explained by differences in the intracellular localization pattern of the dyes. 相似文献
2.
《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1997,1354(3):252-260
A series of meso-5,10,15-tris(N-methyl-4-pyridiniumyl)-20-(4-alkylamidophenyl) porphyrins were synthesized by derivatizing the amino group on the phenyl ring with the following hydrophobic groups: –C(O)C7F15, –C(O)CHCH2, C(O)CH3, –C(O)C7H15, and –C(O)C15H31. The cationic tris-pyridiumyl porphyrin core serves as a DNA binding motif and a photosensitizer to photomodify DNA molecules. The changes of the UV–Vis absorption spectra during the titration of these porphyrins with calf thymus DNA revealed a large bathochromic shift (up to 14 nm) and a hypochromicity (up to 55%) of the porphyrins Soret bands, usually considered as proof of porphyrin intercalation into DNA. Association constants (K) calculated according to the McGhee and von Hippel model, were in the range of 106–107 M−1. An increase in hydrophobicity of the substituents at the 20−meso-position produced higher binding affinity. These porphyrins caused photomodification of the supercoiled plasmid DNA when a green laser beam at 532 nm was applied. Those with higher surface activity acted more efficiently as DNA photomodifiers. The porphyrin with a perfluorinated alkyl chain (–COC7F15) at the meso-20-position inhibited the growth of gram-positive bacteria (S. aureus, or S. epidermidis). Other porphyrins exhibited moderate activity against both gram-negative and gram-positive organisms. 相似文献
3.
In this study, we performed an ultraviolet-visible (UV-Vis) and circular dichroism (CD) spectroscopic analysis of the binary and ternary supramolecular structures formed by self-assembling the following three water-soluble porphyrins with and without a chiral template: the negatively charged, meso-Tetra(4-sulfonatophenyl) porphine (H2TPPS4−); the positively charged meso-trans-(di(N-methyl-4-pyridyl)diphenyl) porphine (trans-DmPyDPP) and meso-cis-(di(N-methyl-4-pyridyl)diphenyl) porphine (cis-DmPyDPP). Polyglutamic acid (both L and D enantiomers) was selected as the chiral template due to its ability to change secondary structure with pH. The propensity for the porphyrins to show an induced CD in the presence of polyglutamic acid is demonstrated. The induced chirality of all supramolecular structures was found to depend on the pH of the solution, the chirality of the polymer, and the order of addition of the positively and negatively charged porphyrins (for ternary complexes). Of particular interest is that the interaction of H2TPPS4− with the chiral scaffold seems to undergo a dynamic rearrangement of the supramolecular structure as evident from the change in the CD spectrum over time. Moreover, experiments with ternary complexes suggest that the preferential interaction of trans-DmPyDPP with the random coil of the polymer shows promise as a sensor of protein secondary structure. 相似文献
4.
Daryono H. Tjahjono Rahmana E. Kartasasmita As’ari Nawawi Shunsuke Mima Takehiro Akutsu Naoki Yoshioka Hidenari Inoue 《Journal of biological inorganic chemistry》2006,11(4):527-538
Interactions of cationic porphyrins bearing five-membered rings at the meso position, meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin (MPzP; M is H2, CuII or ZnII), with synthetic polynucleotides poly(dG-dC)2 and poly(dA-dT)2 have been characterized by viscometric, visible absorption, circular dichroisim and magnetic circular dichroism spectroscopic and melting temperature measurements. Both H2PzP and CuPzP are intercalated into poly(dG-dC)2 and are outside-bound to the major groove of poly(dA-dT)2, while ZnPzP is outside-bound to the minor groove of poly(dA-dT)2 and surprisingly is intercalated into poly(dG-dC)2. The binding constants of the porphyrin and poly(dG-dC)2 and poly(dA-dT)2 are on the order of 106 M−1 and are comparable to those of other cationic porphyrins so far reported. The process of the binding of the porphyrin to poly(dG-dC)2 and poly(dA-dT)2 is exothermic and enthalpically driven for H2PzP, whereas it is endothermic and entropically driven for CuPzP and ZnPzP. These results have revealed that the kind of the central metal ion of metalloporphyrins influences the characteristics of the binding of the porphyrins to DNA.Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users. 相似文献
5.
Diane Marek 《Inorganica chimica acta》2006,359(3):789-799
Two new porphyrins, meso-tris-3,4-dimethoxyphenyl-mono-(4-pyridyl)porphyrin (H2MPy3,4DMPP) and meso-tris-3-methoxy-4-hydroxyphenyl-mono-(4-pyridyl)porphyrin (H2MPy3M4HPP), and their ruthenium analogs obtained by coordination of [Ru(bpy)2Cl]+ groups (where bpy = 2,2′-bipyridine) to the pyridyl nitrogens have been synthesized and studied by electronic absorption spectroscopy, cyclic voltammetry and spectroelectrochemistry. These ruthenated porphyrins couple Ru chromophores to porphyrins containing electroactive meso-substituents. The highest energy electronic absorption for the ruthenated complexes is assigned as a bpy(π) → bpy(π*) intraligand charge transfer while the next lowest energy electronic absorption is assigned as Ru(dπ) → bpy(π*) metal-to-ligand charge transfer (MLCT) transition. The RuIII/II couples occur at approximately 0.95 V versus the SHE reference electrode in acetonitrile solutions. The first oxidation of the porphyrin is localized on the 3,4-dimethoxyphenyl and 3-methoxy-4-hydroxyphenyl substituents, respectively. Electroactive surfaces result from adsorption of these compounds onto glassy carbon electrodes followed by anodic cycling in acidic media. 相似文献
6.
Engelmann FM Mayer I Gabrielli DS Toma HE Kowaltowski AJ Araki K Baptista MS 《Journal of bioenergetics and biomembranes》2007,39(2):175-185
Two series of cationic porphyrins meso-(3N-methylpyridinium)phenylporphyrin (3P1, 3P2c, 3P2t, 3P3 and 3P4) and meso-(4N-methylpyridinium)phenylporphyrin (4P1, 4P2c, 4P2t, 4P3 and 4P4) were studied to obtain a comprehensive understanding of factors
that influence the binding of cationic porphyrins to liposomes and mitochondria, as well as their photodynamic efficiencies
in erythrocytes. Binding and photodynamic efficiency were found to be inversely proportional to the number of positively charged
groups and directly proportional to n-octanol/water partition coefficients (log POW), except for the cis molecules 3P2c and 4P2c. In the cis molecules, binding and photodynamic efficiency were much higher than expected, indicating that specific interactions not
accounted by log POW enhance photodynamic efficiency. The effect of mitochondrial transmembrane electrochemical potentials on cationic porphyrin
binding constants was estimated to be as large as 15%, and may be useful to selectively target this organelle when promoting
photodynamic therapy to induce apoptosis. 相似文献
7.
Vigen G. Barkhudaryan Gayane V. Ananyan Yeva B. Dalyan 《Journal of biomolecular structure & dynamics》2013,31(1)
The influence of water-soluble cationic meso-tetra-(4?N-oxyethylpyridyl)porphyrin (H2TOEPyP4) and it’s metallocomplexes with Ni, Cu, Co, and Zn on hydrodynamic and spectral behavior of DNA solutions has been studied by UV/Vis absorption and viscosity measurement. It was shown that the presence of planar porphyrins such as H2TOEPyP4, NiTOEPyP4, and СuTOEPyP4 leads to an increase in viscosity at relatively small concentrations, and then decrease to stable values. Such behavior is explained by intercalation of these porphyrins in DNA structure because the intercalation mode involves the insertion of a planar molecule between DNA base pairs which results in a decrease in the DNA helical twist and lengthening of the DNA. Further decrease of viscosity is explained by the saturation intercalation sites and occurs outside the binding mode. But, in the case of porphyrins with axial ligands such as CoTOEPyP4 and ZnTOEPyP4, the hydrodynamic parameters decrease, which is explained by self-stacking of these porphyrins in DNA surface. This data are proved by spectral measurements. The results obtained from titration experiments were used for calculation of binding parameters: the binding constant K b and the number of binding sites per base pair n. Obtained data reveal that K b varies between 3.4 and 5.4?×?106?M?1 for a planar porphyrins, a range typical for intercalation mode interactions, and 5.6?×?105?M?1 and 1.8?×?106?M?1 for axial porphyrins. In addition, the exclusion parameter n also testifies that at intercalation, (n~2) the adjacent base pairs are removed to place the planar molecules, and for outside binders to pack on the surface needs too few places (n~0.5–1). It is apparent that the binding is somewhat stronger at intercalation. The viscometric and spectrophotometric measurements are in good agreement. 相似文献
8.
The interaction of meso-tetra(4-N-hydroxyethylpyridyl)porphyrin, meso-tetra(3-N-hydroxyethylpyridyl)porphyrin, and their zinc complexes with bovine serum albumin (BSA) was studied by electronic spectroscopy, CD, and equilibrium dialysis at pH 7.2. The titration of the porphyrins with BSA was accompanied by a decrease in light absorption and a bathochromic shift of the Soret band, as well as by the appearance of an isobestic point. The porphyrin interaction with BSA also led to the induction of positive CD spectra in the visible region, which is explained by the porphyrin sorption on the protein globule. The equilibrium dialysis helped in determining the stoichiometry of binding and the binding constants of the porphyrins under study with BSA using Scatchard plots. This interaction is nonspecific and reversible. 相似文献
9.
B. K. Sharma P. Singh Susheela Sharma 《Journal of enzyme inhibition and medicinal chemistry》2013,28(5):601-607
The antagonistic activities of derivatives of spiroethyl phenyl(substituted)piperazine at the 5-HT1A and adrenergic α1d receptors is quantitatively analyzed employing physicochemical and structural parameters. The derived correlation equation revealed that a substituent, other than 2-CH3 in the phenyl ring, having higher molar refraction, MR, and a substituent producing higher positive field effect at the 3-position are beneficial in increasing the binding affinity at the 5-HT1A receptor. In addition, a less hydrophobic substituent at the 4-position is also helpful in augmenting the binding affinity. The 5-R substituents which have higher MR values, however, elicit a detrimental effect. Two disubstituted compounds which are not present in the original data-set and have higher theoretical binding affinities are designed from the correlation equation. These compounds consisting of 2-OCH(CH3)2, 3-Cl and 2-C3H7, 3-Cl in the phenyl ring, have theoretical pKi values 10.57 and 10.12 respectively. For the adrenergic α1d receptor, a less bulky group at the 3-position with 5-Cl (or simply a 3-Cl) is advantageous in increasing the binding affinity. Likewise, a substituent exhibiting a less negative resonance effect at the 4-position and the substituent with low polarizability and showing more a negative resonance effect at the 5-position are suitable for enhancement of the binding affinity. The analysis provides the grounds for rationalizing substituent selection in designing better potency antagonists in the series. 相似文献
10.
Muhammed Bilaal Ismail Matthew Piers Akerman 《Nucleosides, nucleotides & nucleic acids》2013,32(12):950-971
AbstractHerein, we report the DNA interaction studies of rhenium(I) and -(V) compounds with Schiff base chelates encompassing biologically relevant moieties. More specifically, the DNA interaction capabilities of these rhenium complexes were probed using Gel Electrophoresis and Calf Thymus–DNA titrations monitored by temperature-controlled electronic spectroscopy. The DNA binding modes of the metal compounds were corroborated by molecular docking simulations. In addition, the synthesis and characterization of a novel facial tricarbonyl rhenium(I) compound, fac-[Re(chrs)(CO)3Br], (chrs = {3-{[(2-hydroxyphenyl)imino]methyl}-4H-chromen-4-one) are reported. 相似文献
11.
Tomasz Ostrowski Joanna Zeidler Tomasz Goelizski Bozenna Golankiewicz 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):565-567
Abstract Aryl or tert-butyl substituent in the 6 position of 3,9-dihydro-3-[(2-hydroxy-ethoxy)methyl]-9-oxo-6-R-5H-imidazo[1,2-α]purine 1 directs the benzylation reaction partly into N-4 position to give 3. Cleavage of the third ring of 3 gives 3-benzylacycloguanosine 5, a first 3-aralkilo-9-substituted guanine. 相似文献
12.
Acid-catalyzed condensations of 1,19-diunsubstituted 1,19-dideoxybiladiene-ac dihydrobromides with aldehydes, R · CHO, afford the corresponding meso-substituted porphyrins (R = C6H5, p-Me·C6H4, p-MeO·C5H4, p-O2N·C6H4, p-HOC·C6H4, p-(MeO)2CH·C6H4, Me, n-Pr, CO2Et), mostly in good yield. 相似文献
13.
Lin Wu Li Yang Jing Huang Lixia Zhang Xiaocheng Weng Xiaolian Zhang Chao Shen Xiang Zhou Congyi Zheng 《化学与生物多样性》2009,6(7):1066-1076
A series of cationic ester porphyrins are much more cytotoxic to tumor cells than photofrin, meso‐tetrakis(1‐methylpyridinium‐4‐yl)porphyrin (TMPyP4), and cisplatin. The lowest IC50 value for SGC7901 is ca. 6 nM in vitro with irradiation. These porphyrins also exhibited the most potent photo‐induced cytotoxicity without photobleaching. HeLa Cell apoptosis induced by cationic ester porphyrins after illumination was examined by flow cytometric analysis, staining assays with propidium iodide and annexin V FITC‐PI, and further confirmed by observing morphological changes in the cells. The result of this study indicates that these cationic ester porphyrins may be applied in photodynamic therapy (PDT) in the future. 相似文献
14.
Interaction between tryptophan‐Sm(III) complex and DNA with the use of a acridine orange dye fluorophor probe
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The interaction of the Trp–Sm(III) complex with herring sperm DNA (hs‐DNA) was investigated with the use of acridine orange (AO) dye as a spectral probe for UV‐vis spectrophotometry and fluorescence spectroscopy. The results showed that the both the Trp–Sm(III) complex and the AO molecule could intercalate into the double helix of the DNA. The Sm(III)–(Trp)3 complex was stabilized by intercalation into the DNA with binding constants: K?25°C = 7.14 × 105 L·mol?1 and K?37°C = 5.28 × 104 L·mol?1, and it could displace the AO dye from the AO–DNA complex in a competitive reaction. Computation of the thermodynamic functions demonstrates that ΔrHm? is the primary driving power of the interaction between the Sm(III)(Trp)3 complex and the DNA. The results from Scatchard and viscometry methods suggested that the interaction mode between the Sm(III)(Trp)3 complex and the hs‐DNA is groove binding and weak intercalation binding. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
15.
Amanda M. Slomp Sandra M.W. Barreira Luise Z.B. Carrenho Camila C. Vandresen Ingrid F. Zattoni Stephanie M.S. Ló Juliana C.C. Dallagnol Diogo R.B. Ducatti Alexandre Orsato M. Eugênia R. Duarte Miguel D. Noseda Michel F. Otuki Alan G. Gonçalves 《Bioorganic & medicinal chemistry letters》2017,27(2):156-161
Sixteen porphyrins, including neutral, anionic and cationic meso-(aryl)porphyrins and meso-(1-methyl-4-pyridinium)porphyrins were herein evaluated in terms of their photosensitizing properties against HaCaT keratinocytes. After an initial screening, the cationic porphyrins were studied in more details, by both determining their log POW and performing PDT assays in lower porphyrin concentrations. Porphyrins presenting two or more adjacent positively charged groups, directly linked to the macrocycle meso positions, appeared to be the most effective photosensitizers. The present study also included the dicationic 5,10-diphenyl-15,20-di(1-methylpyridinium-4-yl)porphyrin (14b), which has previously shown promising results on a psoriasis-like in vivo model. Overall results indicated that the beneficial effect related to porphyrins on psoriasis can be related to the decreasing of keratinocyte viability. Furthermore, some of the cationic porphyrins studied appeared as candidates to be utilized as photosensitizers for psoriasis treatment. 相似文献
16.
In this work we investigated the outside binding mode between a cationic porphyrin and a nucleotide pair of DNA, adenine-thymine and guanine-cytosine, in a supramolecular assembly. We used two structural models (semi-extended, extended) that differ in the size of porphyrin, two kinds of theoretical methods: a three layer ONIOM (B3LYP/6-31G(d)/PM3/UFF), and DFT B3LYP/6-31G(d,p), and three cationic porphyrins. ONIOM method was first tested on the semi-extended model that was calculated in four environments: gas phase, solution phase using an explicit solvent model (H2O), in the presence of a sodium cation (Na+) and in both (H2O + Na+). From interaction energy results, we found that the affinity of the cationic substituent by the adenine nucleotide is favored upon the thymine nucleotide. The extended model that considers the whole porphyrin was applied in the gas phase to the four nucleotides. All the cationic porphyrins showed affinity by the nucleotides in the order adenine > guanine > thymine > cytosine. The interaction energy values for outside binding showed a strong porphyrin-nucleotide interaction (≈-90 kcal?mol-1), that slightly varies between the nucleotides suggesting that this kind of cationic porphyrin has a little selectivity for some of them. We also found that the effect of the nature of the cationic substituent (chain length) in the porphyrin on the outside binding is small (≈2–13 kcal?mol-1). Coherence between the results showed that ONIOM is a useful tool to get a reasonable molecular geometry to be used as a starting point in calculations of density functional theory. Figure
A three-layer ONIOM model for the outside binding of cationic porphyrins and nucleotide pair DNA 相似文献
17.
Abstract X-ray, NMR and molecular modeling studies on cyanonaphthridinomycin (C22 H26N4O5), a DNA binding antibiotic, have been carried out to study the structure, conformation and interactions with DNA. The crystals belong to the space group P21 with the cell dimensions of a = 5.934(1), b = 20.684(4), c = 16.866(3)A γ = 90.9° and Z = 4(two molecules/asymmetric unit). The structure was solved by direct methods and difference Fourier methods and refined to an R value of 0.087 for 4061 reflections. The conformation of the molecule is compared with that of naphthridinomycin. There are differences in the orientation of the methoxyl group and the saturated oxazole ring. 1 and 2D NMR studies have been carried out and the dihedral angles obtained from coupling constants have been compared with those obtained from the crystal structure. Molecular mechanics studies were carried out to obtain the energy minimized structure and its comparison with X-ray and NMR results. Molecular modelling studies were performed to propose models for drug-DNA interactions. Both partial intercalation and groove-binding models have been proposed. 相似文献
18.
V. D. Rumyantseva N. V. Roshchina L. D. Fedorova A. F. Mironov V. M. Markushev I. P. Shilov 《Russian Journal of Bioorganic Chemistry》2011,37(6):765-774
The synthesis of asymmetric meso-aryl-substituted porphyrins containing three 4-methoxycarbo-nylphenyl groups, and 4-hydroxyphenyl or 4-hydroxy-3-methoxyphenyl
radicals or isomeric 3-and 4-pyridyl radicals as a forth substitute, is described. 4-Oxyalkyl derivatives are obtained. The
ytterbium complexes of these porphyrins have been synthesized, and their spectral luminescence properties have been studied.
A significant difference in the lifetimes of the excited state of ytterbium complexes of the esters and acids of asymmetric
porphyrins has been shown. 相似文献
19.
Molecular interaction studies between nanoparticles (NPs) and biomolecules are of great importance in the field of nanomedicine as they affect many physiological processes. Therefore, the interaction of zinc sulphide nanoparticles (ZnS NPs) with calf thymus deoxyribonucleic acid (CT DNA) and its significance was analyzed using ultraviolet (UV)–visible light, fluorescence, circular dichroism (CD), zeta potential, viscometry, electrochemical, and polymerase chain reaction methods. Fluorescence quenching analysis revealed that the fluorescence of ZnS NPs was quenched using CT DNA through a static quenching mechanism. The negative values of thermodynamic parameters (ΔG, ΔH, and ΔS) showed that the binding process was spontaneous, exothermic, and van der Waals or hydrogen bonding plays an important role in the interaction of ZnS NPs with CT DNA. Thermal melting (Tm) studies indicated a decrease in the Tm of CT DNA, suggesting the destabilization of CT DNA upon interaction with ZnS NPs. In addition, the results obtained from competitive binding, zeta potential, CD, and viscometry measurements showed that the interaction of ZnS NPs with CT DNA is through groove binding. Electrochemical analysis further confirmed the observed results from various spectroscopic and other related studies, in which decrease in the redox peak current along with changes in peak potential (CV) and increase in the electrical resistance (EIS) indicated the interaction between ZnS NPs and CT DNA. Furthermore, PCR analysis using DNA polymerase revealed the potential of ZnS NPs to inhibit DNA replication in vitro. ZnS NP–CT DNA interaction studies can be explored to define new horizons in biomedical applications of ZnS NPs. 相似文献
20.
Yun Li Nana Wang Dong Lin Xiaohui Liu Yong Yang 《Journal of biomolecular structure & dynamics》2020,38(17):4977-4996
AbstractTwo new nickel (II) triphenylphosphine complexes derived from tridentate aroylhydrazone ligands [H2L1 = 2-hydroxy-3-methoxybenzylidene)benzohydrazone and H2L2 = N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone] and triphenylphosphine were prepared and their molecular structures were determined by single crystal X-ray diffraction analysis. Both nickel(II) complexes showed slightly distorted square planar geometry with one tridentate aroylhydrazone ligand coordinated through ONO donor atoms and one triphenylphosphine ligand coordinated to the nickel center through the phosphorus atom. DNA interaction studies indicated that both complexes possessed higher affinity to herring sperm DNA (HS-DNA) than the corresponding free aroylhydrazone ligand. Molecular docking investigations showed that both complexes could bind to DNA through intercalation of the phenyl rings between adjacent base pairs in the double helix. Meanwhile, bovine serum albumin (BSA) binding studies revealed the complexes could effectively interact with BSA and change the secondary structure of BSA. Further pharmacological evaluations of the synthesized complexes by in vitro antioxidant assays demonstrated high antioxidant activity against NO· and O2˙? radicals. The anticancer activity of each complex was assessed through in vitro cytotoxicity assays (CCK-8 kit) toward A549 and MCF-7 cancer cell and normal L-02 cell lines. Significantly, the Ni(II) complex derived from H2L1 ligand was found to be more effective cytotoxic toward MCF-7cancerous cell with the IC50 value equaled 9.7?μM, which showed potent cytotoxic activity over standard drug cisplatin. Abbreviations A549 human lung carcinoma cell BSA bovine serum albumin CCK-8 Cell Counting Kit-8 DFT density functional theory DNA deoxyribonucleic acid DPPH˙ 2,2-diphenyl-1-picrylhydrazyl H2L1 2-hydroxy-3-methoxybenzylidene)benzohydrazone N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone H2L2 N′-(2-hydroxy-3-methoxybenzylidene)-2-hydroxybenzoylhydrazone HOMO highest occupied molecular orbital IC50 the 50% activity L-02 human normal liver cell LOMO lowest unoccupied molecular orbital (LUMO) MCF-7 human breast carcinoma cell NO˙ nitric oxide O2˙? superoxide anion SOD superoxide dismutase Communicated by Ramaswamy H. Sarma 相似文献