Faculty of Pharmacy, Lj. (FFALJ)
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Sinteza in vrednotenje karbamoil fluoridnih zaviralcev in oksimskih reaktivatorjev butirilholin esteraze = Synthesis and evaluation of carbamoyl fluoride inhibitors and oxime reactivators of butyrylcholinesterase : Uniform Master's Study Programme PharmacyZorman, MašaOrganofosforjeve (OP) spojine predstavljajo veliko nevarnost tako v vojnih razmerah kot tudi za civilno prebivalstvo, saj povzročijo tudi do 3 milijone zastrupitev letno. Mednje na primer spadajo ... različni pesticidi ter živčni bojni strupi razreda G in V. Ti se kovalentno vežejo s katalitičnim Ser200 v človeški acetilholin esterazi in ireverzibilno zavrejo encimsko aktivnost, kar vodi v kopičenje acetilholina v sinapsah, holinergično krizo in na koncu smrt. Kmalu po izpostavljenosti OP je možno encim še reaktivirati z uporabo oksimskih reaktivatorjev – ti so močni nukleofili, ki so zmožni cepiti vezi P-O. V okviru magistrske naloge smo pripravili različne oksimske derivate, ki naj bi selektivno reaktivirali z OP-zavrto človeško butirilholin esterazo (hBChE). Spojini 3 in 5 sta izkazovali primerno afiniteto do hBChE, spojina 5 pa je bila sposobna reaktivirati hBChE, ki je bila zavrta s sarinom in VX. Dokaj visoko afiniteto do hBChE je pokazala spojina 18, neoksimski hidroksipiridinski derivat, ki bi lahko imel večjo sposobnost prehajanja krvno-možganske bariere ter reaktivacije holin esteraz v centralnem živčnem sistemu. Psevdo-ireverzibilni zaviralci holin esteraz karbamatnega tipa se med drugim uporabljajo za profilakso pred zastrupitvami z OP in za zdravljenje Alzheimerjeve bolezni. Pripravili smo fokusirano knjižnico karbamoil fluoridov, ki namesto običajnih fenolov kot izstopajočo skupino vsebujejo fluorid. Sintetizirali smo jih iz sekundarnih aminov z uporabo novega postopka preko N-karbamoilimidazolov. Te spojine so večinoma neselektivno zavirale obe holin esterazi.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [M. Zorman], 2024Language - slovenianCOBISS.SI-ID - 194037507
Author
Zorman, Maša
Other authors
Knez, Damijan, farmacevt |
Meden, Anže
Topics
Organofosforne spojine |
organofosfati |
oksimi |
butirilholin esteraza |
psevdoireverzibilni karbamatni zaviralci |
karbamoil fluoridi
Call number – location, accession no. ... |
Copy status | Reservation |
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Knjižnica emšf 0000000547 ZORMAN MAŠA Sinteza 0000001379 IN: 0018132 Knjižnica emšf 547 ZORMAN MAŠA Sinteza 1379 IN: 0018132 |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Zorman, Maša | 56423 |
Knez, Damijan, farmacevt | 36438 |
Meden, Anže | 53584 |
Source: Personal bibliographies
and: SICRIS
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