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T Theophanides

Publications and source records attributed to T Theophanides.

At least 19 recordsLinked to original sources
PubMed2002

Magnesium-DNA interactions and the possible relation of magnesium to carcinogenesis. Irradiation and free radicals.

Magnesium deficiency causes renal complications. The appearance of several diseases is related to its depletion in the human body. In radiotherapy, as well as in chemotherapy, especially in treatment of cancers with cis-platinum, hypomagnesaemia is observed. The site effects of chemotherapy that are due to hypomagnesaemia are decreased using Mg supplements. The role of magnesium in DNA stabilization is concentration dependent. At high concentrations there is an accumulation of Mg binding, which induces conformational changes leading to Z-DNA, while at low concentration there is deficiency and destabilization of DNA. The biological and clinical consequences of abnormal concentrations are DNA cleavage leading to diseases and cancer. Carcinogenesis and cell growth are also magnesium-ion concentration dependent. Several reports point out that the interaction of magnesium in the presence of other metal ions showed that there is synergism with Li and Mn, but there is magnesium antagonism in DNA binding with the essential metal ions in the order: Zn>Mg>Ca. In the case of toxic metals such as Cd, Ga and Ni there is also antagonism for DNA binding. It was found from radiolysis of deaerated aqueous solutions of the nucleoside 5'-guanosine monophosphate (5'-GMP) in the presence as well as in the absence of magnesium ions that, although the addition of hydroxyl radicals (*OH) has been increased by 2-fold, the opening of the imidazole ring of the guanine base was prevented. This effect was due to the binding of Mg2+ ions to N7 site of the molecule by stabilizing the five-member ring imitating cis-platinum. It was also observed using Fourier Transform Infrared spectroscopy, Raman spectroscopy and Fast Atom Bombardment mass spectrometry that *OH radicals subtract H atoms from the C1', C4' and C5' sites of the nucleotide. Irradiation of 5'-GMP in the presence of oxygen (2.5 x 10(-4) M) shows that magnesium is released from the complex. There is spectroscopic evidence that superoxide anions (O2-*) react with magnesium ions leading to magnesium release from the complex. From radiolysis data it was suggested that magnesium ions can act as radiosensitizers in the absence of oxygen, while in the presence of oxygen they act as protectors and stabilizers of DNA.

Animals↗
PubMed2002

Copper and carcinogenesis.

Metal ions play an important role in biological systems, and without their catalytic presence in trace or ultratrace amounts many essential co-factors for many biochemical reactions would not take place. However, they become toxic to cells when their concentrations surpass certain optimal (natural) levels. Copper is an essential metal. Catalytic copper, because of its mobilization and redox activity, is believed to play a central role in the formation of reactive oxygen species (ROS), such as O2-* and *OH radicals, that bind very fast to DNA, and produce damage by breaking the DNA strands or modifying the bases and/or deoxyribose leading to carcinogenesis. The chemistry and biochemistry of copper is briefly accounted together with its involvement in cancer and other diseases.

Animals↗
PubMed2000

The role of free radical reactions with haemoglobin and thalassaemia.

It is well known that all living systems depend on iron to transport (haemoglobin), store (myoglobin) and utilize (cytochromes, cytochrome oxide) oxygen for respiration. Iron is an essential component in the active sites of the enzyme that protects against oxidation, such as the iron superoxide dismutase, in bacteria and plants. In normal human plasma almost all iron loading of transferrin is 20-30% maximum. In this presentation we review and summarize recent developments in our understanding of iron transport and storage in living systems.

Free Radicals↗
PubMed1996

Molecular modeling of azole antifungal agents active against Candida albicans. 1. A comparative molecular field analysis study.

A series of 56 azole antifungal agents belonging to chemically diverse families related to bifonazole, one of the antimycotic drugs of clinical use, were investigated using the comparative molecular field analysis (CoMFA) paradigm. The studied compounds, which have been already synthesized and reported to be active in vitro against Candida albicans, were divided into a training set and a test set. The training set consisted of 40 molecules from all the different structural classes. Due to the lack of experimental structural data on these derivatives, molecular mechanics techniques were used to obtain putative active conformations for all the compounds. the correctness of this molecular modeling work was confirmed a posteriori by comparison with structural data of the analog 2w obtained by X-ray crystallographic analysis (Massa, S.; et al. Eur. J. Med. Chem. 1992, 27, 495-502). Two different alignment rules of the training set molecules were used in this study and are based on the assumption that according to published results on azole antifungal agents, all the studied compounds exert their inhibitory activity through the coordination of their azole moiety to the protoporphyrin iron atom of the fungal lanosterol 14alpha-demethylase enzyme. The predictive ability of each resultant CoMFA model was evaluated using a test set consisting of 16 representative compounds that belong to all the different structural classes. The best 3D-quantitative structure-activity relationship model found yields significant cross-validated, conventional, and predictive r2 values equal to 0.57, 0.95, and 0.69, respectively. The average absolute error of predictions of this model is 0.30 log units, and the structural moieties of the studied antifungal agents which are thought to contribute to the biological activity were identified. The predictive capability of this model could be exploited in further synthetic studies on antifungal azoles. Furthermore, the results obtained by using two different alignments of the inhibitors suggest that the binding mode of these molecules involves both a coordination to the iron protoporphyrin atom and an additional, likewise relevant, hydrophobic interaction with the active site.

Antifungal Agents↗
PubMed1996

Biological implications of magnesium salts at the molecular level.

The interaction of Mg2+ cations in biological systems is studied by using nucleic acid bases as the biological system. Magnesium salts, such as, MgCl2 6H2O, MgSO4. 7H2O and Mg(ClO4). XH2O have been employed in order to compare their complexation with cytosine and 1-methyl cytosine crystallize in water solutions. The reaction of the above magnesium salts with the two bases has been followed by attempting to crystallization the complexes formed at constant temperature and variable times of crystallization. The water solutions with the above reagents have also been followed by Fourier Transform infrared.

Biological Factors↗
PubMed1993

Design and properties of maxillofacial prosthetic materials.

Maxillofacial reconstruction by prosthetic means is a valuable contribution that medicine offers to the public. Materials design and properties are the main problems faced by scientists in this field. Materials used for intraoral prostheses are not ideal, but they have been perfected to the point of practical use. Denture resins, gold, chromium-cobalt alloys, and porcelain are widely used and produce acceptable results in the oral cavity. In this review, the properties and performance of some polymeric materials used in maxillofacial prosthetics are discussed, and new trends in research and development are also reported.

Humans↗
PubMed1990

The dose rate effects on the in vitro radiolysis products of magnesium-guanosine-5'-monophosphate complexes in aqueous solutions.

This study examined the effects on the radiolysis of magnesium-guanosine-5'-monophosphate complexes in deaerated aqueous solutions, investigated by Fourier transform infrared (FT-IR) spectroscopy. It was found that when the system was irradiated with a dose rate of 500 rad/min (low dose rate), the OH radicals, H atoms and hydrated electrons (eaq-) produced from radiolysis of water reacted mainly by addition to the double bonds C4 = C5 and N7 = C8 of guanine. When the dose rate was 23,800 rad/min (high dose rate) the electrons reacted further with the complex by addition to the carbonyl group, C6 = O, of guanine.

Chemical Phenomena↗
PubMed1990

Possible role of water structure in biological magnesium systems.

Magnesium chloride-water solutions have been studied by Fourier Transform Infrared Spectroscopy (FT-IR) in the near infrared region, 5000-10,000 cm-1. The effect of the concentration of magnesium chloride and temperature on the solutions has been studied from the spectra and it is concluded that magnesium chloride modifies the structure of the bulk water. The important absorption bands of water at 5200 and 7020 cm-1 may be assigned to combination vibrations and overtones. They are shifted either by increasing the magnesium chloride concentration or the temperature. The hydrated magnesium ions, [Mg(H2O)6]2+, will most probably break important hydrogen bonds in the clusters of water (H2O)n, where n = 2, 3, 4, 5, 6.../forming new hydrogen bonds in the presence of hexa-aquated magnesium cations. FAB mass spectra also suggest the formation of hydrated magnesium cations, Mg (H2O)6(2+).

Crystallization↗
PubMed1986

Magnesium-nucleic acid conformational changes and cancer.

The magnesium interaction with the mononucleotide guanosine-5'-monophosphate disodium salt (5'-GMP Na2 or G5'p) has been studied by Fourier transform infrared spectroscopy. The results have been compared with previously obtained proton nuclear magnetic data on the same system as well as other similar systems. The spectra here show that the natural conformation of the mononucleotide changes significantly in the presence of normal concentrations of magnesium chloride (approximately 10(-3) M) from the predominantly C2'-endo,anti into C3'-endo,anti conformation of the sugar ring, and the phosphate group becomes virtually gauche-gauche. The marker bands for C2'-endo,anti and C3'-endo,anti are shown near 820 cm-1 and 803 cm-1, respectively. The infrared spectroscopic results found here indicate that the unit Mg(H2O)2+5 is coordinated at the N7 site of the base guanine and hydrogen bonded via the water molecules to the carbonyl C6 = O and to the phosphate negative oxygens. This type of bonding is very similar to the binding of the antitumor drug cis-platinum, which is chemically (covalently) bound to the N7 site of guanine in the same molecule or in nucleic acids.

Cyclic GMP↗
PubMed1985

Flexibility of DNA and RNA upon binding to different metal cations. An investigation of the B to A to Z conformational transition by Fourier transform infrared spectroscopy.

The interaction of DNA and RNA with Cu(II), Mg(II), [Co(NH3)6]3+ [Co(NH3)5Cl]2+ chlorides and, cis- and trans-Pt(NH3)2Cl2 (CIS-DDP, trans-DDP) has been studied by Fourier Transform Infrared (FT-IR) spectroscopy and a correlation between metal-base binding and conformational transitions in the sugar pucker has been established. It has been found that RNA did not change from A-form on complexation with metals, whereas DNA exhibited a B to Z transition. The marker bands for the A-form (C3'-endo-anti conformation) were found to be near 810-816 cm-1, while the bands at 825 and 690 cm-1 are marker bands for the B-conformation (C2'-endo, anti). The B to Z (C3'-endo. syn conformation) transition is characterized by the shift of the band at 825 cm-1 to 810-816 cm-1 and the shift of the guanine band at 690 cm-1 to about 600-624 cm-1.

Cations↗
PubMed1985

An FT-IR study of DNA and RNA conformational transitions at low temperatures.

Fourier Transform Infrared (FT-IR) spectra of solid samples of DNA and RNA obtained from freeze-drying at solid CO2 and liquid nitrogen temperatures, have been recorded and correlation between the conformational transitions and spectral changes is proposed. It is concluded that an equilibrium exists between A, B and Z conformations at low temperatures for the DNA molecule, which is temperature dependent, whereas the RNA molecule exhibits only the A conformation. The results have been compared with the metal-adducts of DNA and RNA, where one of the conformations is predominant. Marker infrared bands for the B conformer have been found to be the strong band at 825 cm-1 (sugar conformer mode) and a band with medium intensity at 690 cm-1 (guanine breathing mode). The A conformation showed characteristic bands at 810 and 675 cm-1. The B to Z conformational transition was characterized by the strong absorption bands near 820-810 cm-1 and at 665-600 cm-1.

Crystallization↗
PubMed1983

Fourier transform infrared spectra of cells treated with the drug adriamycin.

Fourier Transform Infrared Spectroscopy (FT-IR) is used to study the interaction of adriamycin molecule with DNA and/or cells. For the drug-DNA complexes, the data show that adriamycin interacts not only with the bases pair but also with the sugar-phosphate of DNA within intercalating process. In the case of treated tumor cells, spectra suggest that adriamycin could be interacting also with the proteins of the membrane. The obtained results show that FT-IR is a powerful technique in the study of biological system, say cells.

Candida↗
PubMed1982

Interaction of adriamycin with DNA as studied by resonance Raman spectroscopy.

Raman and resonance Raman spectra of the complex DNA-adriamycin in aqueous solution have been recorded and analysed. Calf thymus DNA was used and it is found that in the complex DNA-adriamycin the chromophore of adriamycin is intercalated in the GC sequences. The substituents on the rings give hydrogen bonding interactions with the base pairs above and below the intercalation site. It is suggested from the Raman and resonance Raman spectral modifications that the phenolic groups of the chromophore are involved in the drug-DNA intercalation, in addition to pi-pi, hydroxyl and amino group interactions.

Animals↗
PubMed1981

Binding of the anticancer drug cis-dichlorodiammineplatinum to 3'(2')-guanosine monophosphate and nucleic acids.

The UV-absorption spectral characteristics of cis[Pt(NH3)2(GMP)2]-2 ([Pt(NH3)2 (Guanosine-3'(2')-monophosphate)2]-2) (abbreviated Pt (GMP)2) and cis-[Pt(NH3)2(Guanine)2]+2 (abbreviated Pt(Gua)2) were studied at acidic, neutral and alkaline pH values. The compound Pt(GMP)2 was formed by reacting GMP with cis-Pt(NH3)2Cl2(= cis-platinum) in H2O(pH approximately 6) at 24 degrees C for 7 days in the dark. Hydrolysis of Pt(GMP)2 with HClO4 to remove its sugar-phosphate moiety followed by paper chromatographic separation yielded Pt(Gua)2. Exposure to alkali did not cause any irreversible change in the absorption spectrum of Pt(GMP)2 indicating the lack of imidazole ring fission. Spectral changes for Pt(Gua)2 as compared to control Gua at neutral and alkaline pH values were quantitatively less than those reported for 7-methyl guanine in the literature. Electronic perturbation of the guanine ring system was thus found to be considerably less for platinum than for alkylation of the N7 site. These subtle differences between the platination and alkylation of Gua are of interest in view of the apparent similarities between the biological effects of cis-platinum and bifunctional alkylating agents reported in the literature.

Alkylation↗
PubMed1979

Preferential interstrand cross-linking of DNA rich in guanine and cytosine by cis-dichlorodiammineplatinum(II).

Two native DNAs differing in G + C content were bound equally with the antitumour drug cis-Pt(NH3)2Cl2 at increasing Pt/P ratios. Resulting changes in their ultraviolet absorption spectra show equal fractional decreases in the initially different values of A250/A270 for the two DNAs, and less prominent bathochromic and hyperchromic shifts for DNA richer in G + C. Changes in the absorbance (A260) observed before and after subjecting the DNA samples to the conditions of denaturation (with alkali) and renaturation, indicate the following effects of the platinum binding. Maximum renaturation occurs at 50% lower Pt/P ratio of 0.03 for Micrococcus lysodeikticus DNA (72% G + C) than 0.06 for salmon sperm DNA (41% G + C) and is maintained at higher Pt/P ratios. Interstrand cross-links that facilitate renaturation, cause an incomplete melting of DNA so that the platinum-DNA complex at pH 12.5 has a reduced absorbance. This effect is more evident for the platinum complex with DNA richer in G + C due to more interstrand cross-links. Platinum-induced destabilisation of DNA, shown by its hyperchromicity at the pre-melting state (pH 6--7, 25 degrees C) and also by a lowering of the pH corresponding to the mid-point of its melting, is less evident for DNA richer in G + C.

Animals↗
PubMed1976

Differentiation between chelated and non-chelated DNA-Pt complexes by atomic absorption spectrophotometry.

As a continuation of our study of the properties of the cis-trans platinum series we have investigated the DNA-Pt complexes of [Pt(dien)Cl]Cl, cis-Pt (en)Cl2, cis-Pt (NH3)2Cl2 and K2[PtCl4] by atomic absorption spectrophotometry. The DNA-Pt complexes correspond to the saturation of the N7-(Guanine) sites. It has been found that the chelate complexes obtained with cis-Pt(en)Cl2, cis-Pt(NH3)2Cl1 and K2[PtCl4] show the same absorbance. The [Pt(dien)Cl]Cl and trans-Pt (NH3)2Cl2 which are bound to the N7 (tuanine) site only, show an absorbance greater than the chelate complexes by a factor of two. In addition, it has been possible in the case of the trans-Pt (NH3)CCl1 complex to follow the fixation of platinum to DNA by atomic absorption spectrophotometry. The result is similar to the ionic chlorine liberation procedure reported previously.

Binding Sites↗