20.500.12556/RUL-158588 Kromatografsko določanje topnosti in stabilnosti spojin vodnic Chromatographic determination of solubility and stability of lead compounds Proces razvoja do ustrezne zdravilne učinkovine z želenimi lastnostmi je finančno in časovno obremenjujoč proces. Raziskovanje v industriji se začne z rešetanjem visoke zmogljivosti, s katerim lahko pridemo do spojin vodnic. Spojina vodnica je naravna, polsintezna ali sintezna spojina z ustreznim farmakološkim in biološkim delovanjem. Spojine vodnice so si med seboj podobne, vendar se razlikujejo v strukturi, fizikalno-kemijskih lastnostih, učinkovitosti delovanja, afiniteti do tarče in podobno. V magistrski nalogi smo se osredotočili predvsem na vidika topnosti in metabolizma teh spojin vodnic, ki nam bosta omogočala boljši vpogled v ustreznost sintetizirane spojine kot potencialne zdravilne u inkovine. Preko parametrov topnosti in metabolizma spojin vodnic lahko v grobem sklepamo, ali ima ta spojina potencial in ali je primerna za nadaljnjo optimizacijo. Topnost in metabolizem smo dokazovali z analitsko metodo tekočinske kromatografije visoke ločljivosti z UV-Vis detekcijo. Za dokazovanje topnosti smo uporabili sedemtočkovno umeritveno premico, da smo pokrili čim večje koncentracijsko območje, v katerem bi lahko potrdili natančnost in točnost rezultatov. Pri metabolizmu smo poleg spojine vodnice dnevno izvajali tudi vzporedni test metabolizma testosterona, ki je služil kot kontrola za ustreznost postopka in orodje, s katerim smo lahko vrednotili rezultate metabolne stabilnosti spojin vodnic. Ugotovili smo, da so testirane spojine relativno slabo topne, vendar metabolno stabilne, kar bo omogočalo načrtovanje novih analogov teh spojin z izboljšanimi lastnostmi. The process of developing a suitable active ingredient with the desired properties is a financially and time-consuming process. Industry research begins with high-throughput screening to arrive at lead compounds. A lead compound is a natural, semi-synthetic or synthetic compound with pharmacological and biological activity. Lead compounds are similar to each other, but slightly differ in structure, physico-chemical properties, efficiency of action, affinity to the target, and the like. In the master's thesis, we mainly focused on the solubility and metabolism aspects of these lead compounds, which will give us a better insight into the relevance of the synthesized compound as a potential medicinal agent. Through the solubility and metabolism parameters of lead compounds, we can roughly conclude whether this compound has potential and whether it is suitable for more detailed research. Solubility and metabolism were demonstrated using the analytical method of high-resolution liquid chromatography on a Thermo-Fischer UPLC system in the premises of the Faculty of Pharmacy. To evaluate solubility, we have used a seven-point calibration curve to cover as large a concentration range as possible in which we could claim the precision and accuracy of the results. In metabolism, in addition to the lead compound, we also performed a parallel test of testosterone metabolism daily, which served as a control for the adequacy of the procedure and a tool with which we could evaluate the results of the metabolic stability of lead compounds. We found that the tested compounds are relatively poorly soluble, but metabolically stable, which will enable the design of new analogues of these compounds with improved properties. spojina vodnica kineti na topnost termodinamska topnost metabolizem HPLC. lead compound kinetic solubility thermodynamic solubility metabolism HPLC. true false false Slovenski jezik Angleški jezik Magistrsko delo/naloga 2024-06-16 07:45:42 2024-06-16 07:45:45 2024-07-01 03:39:00 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 105029 21012.pdf 21012.pdf 1 4D6B9940FC7B9594D8F2BFD115960F16 651e2abb9045aeadd033f695598ed1df9d1cd5a4a248f30a3d977035d53736d2 af5e6d51-2ba3-11ef-9bcc-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=186264 Fakulteta za farmacijo 0 0 0