20.500.12556/RUL-162749 Sistematični pristop k encimsko kataliziranim transformacijam resveratrola Systematic approach towards enzyme-catalyzed transformations of resveratrol Resveratrol sodi v skupino polifenolov in se nahaja v plodovih številnih sadežev kot so grozdje, borovnice in brusnice. Povezujejo ga z izrazom »francoski paradoks«, ki opisuje korelacijo med uživanjem rdečega vina in zmanjšano pojavnostjo srčno-žilnih bolezni. Največjo omejitev pri uporabi resveratrola predstavlja nizka biološka uporabnost, saj se v telesu hitro pretvori v glukoronide in izloči. Do sedaj je bilo sicer izvedenih že precej kliničnih študij, ki so dokazovale biološke učinke resveratrola pri različnih odmerkih resveratrola na časovno enoto. Z namenom izboljšanja učinkovitosti in biološke uporabnosti resveratrola so bile narejene številne kemijske modifikacije resveratrola z encimsko kataliziranimi reakcijami, ki delujejo na principu aciliranja. Z aciliranjem na mestih 3,5,4' (kjer je prisotna OH skupina) so pripravili različne derivate in primerjali njihovo učinkovitost v primerjavi z resveratrolom. Prav tako je bilo precej dela narejenega na selektivnem aciliranju na 4'-O mestu in na konverziji do di- ali triacetatov. Pri tem so bila uporabljana številna različna topila in donorji acilne skupine, in sicer z različnimi lipazami ter z navadnim stresalnikom ali v ultrasonični kadički. Z namenom potrditve istovetnosti in preučitve prej omenjenih parametrov na pretvorbe resveratrola smo se v magistrski nalogi osredotočili na reakcije, pri katerih smo uporabljali dva encima, in sicer encim Candida antarctica lipaze B (CALB) in encim Burkholderia cepacia lipaze, poznan tudi pod imenom Pseudomonas cepacia lipaza (PCL ali PS). Kot donorje acilne skupine smo uporabili vinil acetat, vinil lavrat ter vinil propionat. Z namenom ugotovitve, katero topilo deluje najbolje pri encimsko kataliziranih reakcijah, je bil narejen t.i. 'solvent screening' oziroma preverba topil, s katerim smo ugotovili, da je diizopropil eter najbolj primeren. Rezultati aciliranja so pokazali, da smo pri vseh treh donorjih acilne skupine pripravili diaciliran produkt (3,4'-O substituiran). Resveratrol belongs to the group of polyphenols, present in many fruits, and is associated with the expression "French paradox", which describes the correlation between the consumption of red wine and the reduced incidence of cardiovascular diseases. The biggest limitation of resveratrol is its low bioavailability, as it is quickly converted into glucuronides in the body and therefore rapidly excreted. A number of clinical studies performed have demonstrated beneficial effects of resveratrol at different dosages of resveratrol per time unit tested. In order to improve the effectiveness and bioavailability of resveratrol, many chemical modifications of resveratrol were carried out with enzyme-catalyzed acylations. By acylation at the positions 3,5,4' (where the OH group is present), several derivatives were prepared and their efficacy compared with resveratrol. Research was also focused on selective acylation at the 4’-O position, as well as conversion of resveratrol to di- or triacetates. Many different solvents and acylating donors were used, together with different lipases and with either a regular shaker or in an ultrasonic bath. To confirm the outcomes of previous experiments and examine new parameters, within the thesis we focused on two enzymes, namely CALB and lipase PS. Vinyl acetate, vinyl laurate and vinyl propionate were used as acylating donors. To determine the most optimal solvent for enzyme-catalyzed reactions, the so-called "solvent screening" was performed, and diisopropyl ether was found to be the most appropriate. The results of acylation reactions showed that with all three acylating donors, a diacylated product (3,4'-O substituted) was obtained. The reaction conditions to afford the acylated derivatives were investigated and are discussed in this thesis. resveratrol encimsko katalizirano aciliranje preverba topil donorji acilne skupine lipaza PS CALB resveratrol enzyme-catalyzed acylation solvent screening acylating donors lipase PS CALB true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2024-09-27 07:45:08 2024-09-27 07:45:19 2024-10-01 03:38:08 0000-00-00 00:00:00 2024 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 111060 24919.pdf 24919.pdf 1 8CDA5F362C1E27C34B403F6391FEEA86 9cdbbea42e566e2ee4939e6aa1f9bc65869bfb08864a501135432daadb5eb765 8f2b4493-7c93-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=192170 Fakulteta za farmacijo 0 0 0