Preparation, redox properties and biological activity of ferrocene-nucleobase derivatives
| Autor: | Toma, Mateja |
|---|---|
| Přispěvatelé: | Vrček, Valerije, Djaković, Senka |
| Jazyk: | chorvatština |
| Rok vydání: | 2022 |
| Předmět: |
redoks svojstva
PRIRODNE ZNANOSTI. Kemija. Organska kemija NATURAL SCIENCES. Chemistry. Organic Chemistry ROS nucleobases DFT calculations ferocenski derivati ferrocene derivatives redox properties nukleobaze citotoksični učinak udc:54(043.3) DFT izračuni Kemija. Kristalografija. Mineralogija cytotoxic activity Chemistry. Crystallography. Mineralogy |
| Popis: | U okviru ove doktorske disertacije pripravljeni su, te eksperimentalnim i teorijskim metodama istraženi, novi ferocenski derivati različito supstituiranih purinskih nukleobaza s karbonilnom poveznicom između heterocikličkog i organometalnog dijela. Ferocenoil-purinski derivati 1-31 pripravljeni su reakcijom između purinskog aniona i ferocenoil-klorida pri čemu su, ovisno o C6 ili C2 supstituentima na nukleobazi, nastali N7 i N9 regioizomeri, ili isključivo N9 produkti. Pripravljeni su spojevi karakterizirani spektroskopskim i elektrokemijskim metodama (NMR, IR, UV-Vis, CV i SWV) te spektrometrijom masa (MS), ispitano je njihovo in vitro citotoksično djelovanje na L929 staničnim linijama i na humanim tumorskim staničnim linijama (A549, HepG2, PANC-1, MCF-7) te sposobnost stvaranja ROS-a kao mogućeg mehanizma citotoksičnosti. Teorijskim su pristupom uz upotrebu DFT izračuna opisana fizikalno-kemijska svojstava ferocenskih derivata nukleobaza, definirani su pogodni modeli za opis njihovih elektrokemijskih svojstva,te je objašnjen reakcijski mehanizma njihova nastanka i opisana transacilacija u organskim otapalima. Pripravljeni su spojevi elektrokemijski aktivni i stvaraju ROS acelularno i celularno. Spojevi 11 i 12 pokazali su izraženi citotoksični učinak na svim ispitanim staničnim linijama, a slijede spojevi 3 i 4, dok je spoj 26 selektivno citotoksičan za HepG2 stanice. Rezultati ovog istraživanja dobiveni povezivanjem eksperimentalnog i teorijskog pristupa, proširuju spektar pripravljenih i ispitanih redoks aktivnih ferocenoil-purinskih spojeva kao potencijalnih citostatskih agenasa. In the framework of this doctoral dissertation, new ferrocene derivatives containing variously substituted purine nucleobases with a carbonyl bond between the two parts were prepared and investigated by the experimental and theoretical methods. Ferrocenoyl-purine derivatives 1-31 were prepared by nucleophilic substitution reaction on the carbon atom of the carbonyl group of ferrocenoyl-chloride with purine nucleobase anion generated by the deprotonation with a strong base. Regioselectivity and regiospecificity of reaction were strongly influenced by the C6 or C6, C2 substituents of the purine ring. The compounds were characterized by spectroscopic, spectrometric, and electrochemical methods (NMR, IR, UV-Vis, MS, CV and SWV) and screened in an in vitro cytotoxic assay against L929 cell lines and human cancer cell lines (A549, HepG2, PANC-1, MCF-7). The ability to generate ROS was measured as a possible mechanism of cytotoxic action. Using a theoretical approach by the means of DFT calculations, the physicochemical properties of ferrocene-nucleobase derivatives were predicted and described, the reaction mechanism of their formation was resolved as well as the transacylation in DMSO. Prepared compounds showed to be electrochemically active and form ROS in both acellular and cellular media. Compounds 11 and 12 showed enhanced cytotoxic effect against all tested cell lines, followed by compounds 3 and 4, while compound 26 showed selective cytotoxic effect against HepG2 cell line. The results of this study obtained by combination of experimental and theoretical approaches, expand the range of prepared and tested redox active ferrocenoyl-purine compounds as potential cytostatic agents. |
| Databáze: | OpenAIRE |
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