Study of interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity
Background1,4-dihydropyridines (1,4-DHP) possesses important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. It was shown that the antimutagenic 1,4-dihydropyridine AV-153-Na interacts with DNA. The aim of the current study was to test the capability of the compound to scavenge peroxynitrite and hydroxyl radical, to test intracellular distribution of the compound, and to assess the ability of the compound to modify the activity of DNA repair enzymes and to protect the DNA in living cells against peroxynitrite-induced damage.MethodsPeroxynitrite decomposition was assayed by UV spectroscopy, hydroxyl radical scavenging—by EPR spectroscopy. DNA b…
Tight DNA-protein complexes isolated from barley seedlings are rich in potential guanine quadruplex sequences
Background The concept of chromatin domains attached to the nuclear matrix is being revisited, with nucleus described as a set of topologically associating domains. The significance of the tightly bound to DNA proteins (TBP), a protein group that remains attached to DNA after its deproteinization should be also revisited, as the existence of these interactions is in good agreement with the concept of the topologically associating domain. The work aimed to characterize the DNA component of TBP isolated from barley seedlings. Methods The tight DNA-protein complexes from the first leaves, coleoptiles, and roots of barley seedlings were isolated by purification with chromatography on nitrocell…
Metal ions modify DNA-protecting and mutagen-scavenging capacities of the AV-153 1,4-dihydropyridine.
Abstract 1,4-Dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. AV-153-Na, an antimutagenic and DNA-repair enhancing compound was shown to interact with DNA by intercalation. Here we studied DNA binding of several AV-153 salts to evaluate the impact of AV-153 modifications on its DNA binding capacity, the ability to scavenge the peroxynitrite, to protect HeLa and B-cells cells against DNA damage. Affinity of the AV-153 salts to DNA measured by a fluorescence assay was dependent on the metal ion forming a salt in position 4 of the 1,4-DHP, and it decreased as follows: Mg > Na > Ca > Li > Rb > K. AV-153-…
New 1,4-Dihydropyridines Down-regulate Nitric Oxide in Animals with Streptozotocin-induced Diabetes Mellitus and Protect Deoxyribonucleic Acid against Peroxynitrite Action.
Diabetes mellitus (DM) and its complications cause numerous health and social problems throughout the world. Pathogenic actions of nitric oxide (NO) are responsible to a large extent for development of complications of DM. Search for compounds regulating NO production in patients with DM is thus important for the development of pharmacological drugs. Dihydropyridines (1,4-DHPs) are prospective compounds from this point of view. The goals of this study were to study the in vivo effects of new DHPs on NO and reactive nitrogen and oxygen species production in a streptozotocin (STZ)-induced model of DM in rats and to study their ability to protect DNA against nocive action of peroxynitrite. STZ…
DNA-binding studies of a series of novel water-soluble derivatives of 1,4-dihydropyridine
Aim. to determine DNA interaction modes for a series of 1,4-dihydropyridines with different biological activities synthesized in the Latvian Institute of Or-ganic Synthesis. Methods. Affinity of the compounds to DNA was detected by UV/VIS spec-trometry and re-proofed by means of spectrofluorimetry, EBr extrusion assay, cyclic voltammetry and DNA melting. Radical scavenging was tested by electron paramagnetic resonance spectros-copy, peroxynitrite binding was monitored spectrophotometrically, protection of DNA against hydroxyl radical was determined by gel electrophoresis. Results. In a series of water-soluble monocyclic derivatives of 1,4-dihydropyridine with carboxylate groups in position-…
Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats
Abstract Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effec…
Spectroscopic and electrochemical study of interactions between DNA and different salts of 1,4-dihydropyridine AV-153
1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antimutagenic and DNA-binding activity. The latter activity was first described for water-soluble 1,4-DHP with carboxylic group in position 4, the sodium salt of the 1,4-DHP derivative AV-153 among others. Some data show the modification of physicochemical properties and biological activities of organic compounds by metal ions that form the salts. We demonstrated the different affinity to DNA and DNA-protecting capacity of AV-153 salts, depending on the salt-forming ion (Na, K, Li, Rb, Ca, Mg). This study aimed to use different approaches to collate data on the DNA-binding mode of AV-153-N…
Spectrophotometric study of DNA interactions with ftorafur and its elementoorganic derivatives
ABSTRACTFtorafur is an antimetabolite antitumour drug successfully used for treatment of various tumours. It is generally accepted that ftorafur is converted to 5-fluoruracil. However, some data indicate direct interactions of the compound with DNA. To test this hypothesis we have performed spectrophotometric study of DNA interactions of ftorafur and some of its elementoorganic derivatives with DNA. UV-VIS spectra of the tested compounds were recorded in absence and presence of increasing amounts of DNA. DNA caused a hypochromic effect in spectra of ftorafur, similar, but weaker effect was observed in 5-fluoruracil spectra. Trimethylgermyl derivative of ftorafur manifested a higher DNA-bind…
Interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA and DNA-damaging molecules and its impact on DNA repair activity
1,4-dihydropyridines (1,4-DHP) possess important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. Interaction of some 1,4-DHP with DNA was recently reported. AV-153-Na, an antimutagenic and DNA-repair-enhancing compound appeared to be able to interact with DNA by intercalation. The aim of the current study was to characterize DNA’s capacity for the binding of AV-153-Na, and using different approaches, to test intracellular distribution of the compound, to test the ability of the compound to scavenge peroxynitrite and hydroxyl radical and to assess the ability of the compound to modify the activity of DNA repair enzymes. The DNA binding activity…