1,4 Dihidropiridīnu, aziridīnamīdoksīmu un modificētu nukleozīdu mijiedarbība ar DNS
Date
2012
Authors
Štēbele, Kristiāna
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Spēju interkalēt starp DNS pavedieniem uzskata par vielas citotoksiskās vai
mutagēnās darbības pazīmi. Pēdējos gados parādās dati par antimutagēnu vielu interkalāciju
DNS. Darba mērķis bija izpētīt antimutagēnā 1,4-dihidropiridīna AV-153 un tā analogu, kā arī
Latvijas Organiskās Sintēzes Institūtā sintezētu aziridīnamīdoksīmu un metālu-modificētu
ftorafura atvasinājumu mijiedarbību ar DNS. Darbā izmantotas spektrofotometrijas,
spektrofluorimetrijas, gēla elektroforēzes metodes. Tika pierādīts, ka AV-153 interkalē starp
DNS pavedieniem, vienpavediena pārrāvuma vietā, kā arī spēj mijiedarboties ar
vienpavediena DNS. Ftorafurs un tā atvasinājumi tieši mijiedarbojas ar DNS.
Atslēgas vārdi: DNS, mijiedarbība, interkalācija, 1,4-dihidropiridīni, ftorafurs.
Ability to intercalate between DNA strands determines cytotoxic or mutagenic activity of substance. In recent years intercalating activity was also reported for some antimutagenic substances. The aime of this work was to study interactions with DNA of the antimutagenic 1,4-dihydropyridine – AV-153 and its analogues, aziridin-1-il oximes and metal-modified derivatives of ftorafur with different biological activities synthesized in Latvian Institute of Organic Synthesis using spectrophotometric, spectrofluorimetric and gel electrophoresis analysis methods. Main findings of this work – AV-153 intercaletes between DNA strands. Furthermore, it also binds to a single strand DNA, but it intercalates between two adjacent CG base pairs in a DNA duplex. Ftorafur, its derivatives and 5-fluoruracil binds dirrectly to DNA. Key words: DNA, interaction, intercalation, 1,4-dihydropyridines, ftorafur.
Ability to intercalate between DNA strands determines cytotoxic or mutagenic activity of substance. In recent years intercalating activity was also reported for some antimutagenic substances. The aime of this work was to study interactions with DNA of the antimutagenic 1,4-dihydropyridine – AV-153 and its analogues, aziridin-1-il oximes and metal-modified derivatives of ftorafur with different biological activities synthesized in Latvian Institute of Organic Synthesis using spectrophotometric, spectrofluorimetric and gel electrophoresis analysis methods. Main findings of this work – AV-153 intercaletes between DNA strands. Furthermore, it also binds to a single strand DNA, but it intercalates between two adjacent CG base pairs in a DNA duplex. Ftorafur, its derivatives and 5-fluoruracil binds dirrectly to DNA. Key words: DNA, interaction, intercalation, 1,4-dihydropyridines, ftorafur.
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Keywords
Farmācija