prikaz prve stranice dokumenta Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze
Embargo period 2025-01-17
doctoral thesis
Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze
Zagreb: University of Zagreb, Faculty of Science, 2023. urn:nbn:hr:217:838768
Matošević, Ana
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Matošević, A. (2023). Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze (Doctoral thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:838768

Matošević, Ana. "Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze." Doctoral thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:838768

Matošević, Ana. "Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze." Doctoral thesis, University of Zagreb, Faculty of Science, 2023. https://urn.nsk.hr/urn:nbn:hr:217:838768

Matošević, A. (2023). 'Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze', Doctoral thesis, University of Zagreb, Faculty of Science, accessed 25 November 2024, https://urn.nsk.hr/urn:nbn:hr:217:838768

Matošević A. Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze [Doctoral thesis]. Zagreb: University of Zagreb, Faculty of Science; 2023 [cited 2024 November 25] Available at: https://urn.nsk.hr/urn:nbn:hr:217:838768

A. Matošević, "Dizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze", Doctoral thesis, University of Zagreb, Faculty of Science, Zagreb, 2023. Available at: https://urn.nsk.hr/urn:nbn:hr:217:838768

Metadata
TitleDizajn, sinteza i biološka evaluacija biskarbamata kao potencijalnih selektivnih inhibitora butirilkolinesteraze
Title (english)Design, synthesis and biological evaluation of biscarbamates as potential selective inhibitors of butyrylcholinesterase
AuthorAna Matošević
MentorAnita Bosak (mentor)
Committee memberJasmina Rokov Plavec (predsjednik povjerenstva)
Committee memberVesna Petrović-Peroković (član povjerenstva)
Committee memberDanijela Barić (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2023-01-17, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Universal decimal classification
(UDC)		54 - Chemistry. Crystallography. Mineralogy
Abstract
Inhibicija butirilkolinesteraze (BChE) predstavlja novi, obećavajući pristup liječenju Alzheimerove bolesti (AB). U sklopu ove disertacije dizajnirani su i sintetizirani biskarbamati s različito supstituiranim atomima dušika karbamatnih skupina i 1-hidroksi-2-aminoetilnog lanca. Za 25 biskarbamata određena je sposobnost inhibicije ljudske BChE i acetilkolinesteraze (AChE), procijenjena je sposobnost prelaska krvno-moždane barijere pasivnim transportom, in vitro toksičnost prema jetrenim, bubrežnim i živčanim stanicama te sposobnost kelatiranja biometala Cu2+, Zn2+ i Fe2+. Svi ispitivani biskarbamati pokazali su vremenski ovisnu inhibiciju s konstantama brzine inhibicije od 103−106 mol-1 dm3 min-1i općenito većom selektivnošću prema BChE u odnosu na AChE. Za tri biskarbamata utvrđena je mogućnost prolaska krvnomoždane barijere pasivnim transportom, dok je za njih devet ta sposobnost ograničena. Većina biskarbamata nije pokazala citotoksični učinak prema odabranim staničnim linijama, dok su svi pokazali sposobnost kelatiranja najmanje jednog od ispitanih iona biometala. Radi visoke BChE selektivnosti, netoksičnosti, sposobnosti kelatiranja biometala i prolaska krvno-moždane barijere, za daljnji razvoj kao lijekova za liječenje kasnijih stadija AB istaknula su se tri spoja (3, 9 i 26).
Abstract (english)
Inhibition of butyrylcholinesterase (BChE) represents a new, promising approach to the treatment of Alzheimer's disease (AD). As part of this dissertation, biscarbamates with different substituted nitrogens of carbamate groups and 1-hydroxy-2-aminoethyl chain were designed and synthesized. For 25 biscarbamates, the ability to inhibit human BChE and acetylcholinesterase (AChE) was determined, the ability to cross the blood-brain barrier (BBB) by passive transport, in vitro toxicity to liver, kidney and neural cells and the ability to chelate biometals Cu2+, Zn2+ and Fe2+ were evaluated. All of the tested biscarbamates showed a timedependent inhibition with inhibition rate constants in 103 − 106 mol-1 dm3 min-1 range with a generally higher preference for BChE compared to AChE. For three biscarbamates it was found that they should be able to cross the BBB by passive transport, while this ability was limited for nine biscarbamates. Most of the biscarbamates did not show a cytotoxic effect against the selected cell lines. All of the biscarbamates were shown to have the ability to chelate at least one of the biometals. Due to the high BChE selectivity, non-toxicity, ability to chelate biometals and pass the BBB, three compounds (3, 9 and 26) were pointed out for further development as drugs for the treatment of later stages of AD.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:838768
Promotion2023
ProjectNumber: IP-2018-01-7683
Title: Analiza interakcija butirilkolinesteraze s novim inhibitorima i reaktivatorima
Acronym: AnalyseBChE
Leader: Zrinka Kovarik
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: IP
ProjectNumber: IP-2020-02-9343
Title: Razvoj bioaktivnih molekula za tretman neurodegenerativnih bolesti
Title: Development of Bioactive Molecules for Neurodegenerative Diseases Treatment
Acronym: BioMol4ND
Leader: Anita Bosak
Jurisdiction: Croatia
Funder: HRZZ
Funding stream: IP
Study programmeTitle: Doctoral study in chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija (doktor/doktorica znanosti, područje prirodnih znanosti, polje kemija)
Type of resourceText
Extent119 str. ; 30 cm
File originBorn digital
Access conditionsEmbargoed access
Embargo expiration date: 2025-01-17
Terms of useLicence In copyright icon
Created on2023-02-03 14:31:43