Preparation and biological evaluation of novel hydroxypiridinone derivatives
| Autor: | Dandić, Andrea |
|---|---|
| Přispěvatelé: | Petrović-Peroković, Vesna |
| Jazyk: | chorvatština |
| Rok vydání: | 2022 |
| Předmět: |
antiproliferative activity
adamantan adamantane structureactivity relationship study odnosa strukture i aktivnosti 3-hydroxypyridin-4-ones PRIRODNE ZNANOSTI. Kemija NATURAL SCIENCES. Chemistry lipofilnost antiproliferativna aktivnost 3-hidroksipiridin-4-oni istraživanja odnosa strukture i aktivnosti lipophilicity udc:54(043.3) istraživanja Kemija. Kristalografija. Mineralogija Chemistry. Crystallography. Mineralogy |
| Popis: | U ovoj doktorskoj disertaciji opisana je priprava novih derivata N-aril-3-hidroksipiridin-4-ona koji se razlikuju po strukturi supstituenata vezanih u meta- i para-položaj arilnog dijela molekule. Reakcije su provedene zagrijavanjem vodenih otopina polaznih reaktanata, maltola i meta- i para-supstituiranih anilina u autoklavu. Odabrani para-supstituirani N-aril-3- hidroksipiridin-4-oni uspješno su sintetizirani i u uvjetima mikrovalne sinteze. Pripravljeni 3- hidroksipiridin-4-oni dodatno su strukturno modificirani uvođenjem lipofilnih podjedinica u njihovu strukturu s naglaskom na adamantilnoj podjedinici. Na piranonski dio molekule 3- hidroksipiridin-4-ona adamantilna podjedinica vezana je esterskim i eterskim tipom veze dok je na meta- i para-položaj arilnog dijela molekule vezana esterskom i amidnom vezom. U disertaciji je opisana i biološka evaluacija pripravljenih spojeva. Ispitivana su antiproliferativna svojstva pripravljenih spojeva te je sustavno istražen odnos strukture i biološke aktivnosti (engl. Structure-Activity Relationship, SAR). Na temelju dobivenih rezultata izdvojeni su najpotentniji spojevi (engl. lead compound) pri čemu je uzet u obzir njihov selektivni antiproliferativni učinak. In this thesis preparation and structural modification of novel N-aryl 3-hydroxypyridin-4-one derivatives is described. Prepared compounds are distinguished by position and structure of substituent on the aryl part of the molecule. Reactions were conducted with heating of aqueous solutions of starting materials, maltol and meta- and para-substituted anilines, in autoclave. Selected para-substituted N-aryl 3-hydroxypyridin-4-ones were successfully prepared in conditions of microwave synthesis. Prepared 3-hydroxypyridin-4-ones were additionally structurally modified by incorporating lipohilic units into pyridinone structure, primarily adamantyl unit. On the pyranone part of the molecule adamantyl unit was introduced by ester and ether bond type and by using ester and amide bond in meta and para position of the aryl part of the molecule. Antiproliferative activity of prepared compounds was examined and structure-activity relationship was systematically researched. On the basis of obtained results lead compounds were singled out whereby selective activity of compounds towards tumor versus normal cell lines was considered. |
| Databáze: | OpenAIRE |
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