ALL libraries (COBIB.SI union bibliographic/catalogue database)
-
Sinteza derivatov zaviralca encima InhA pirolnega tipa ter kiralna ločba izbranih zaviralcev InhA in imunoproteasoma = Synthesis of pyrrole type derivatives as InhA inhibitors and chiral separation of selected InhA and immunoproteasome inhibitors : enoviti magistrski študijski program FarmacijaSinjur, AnjaTuberkuloza je stara, nalezljiva in lahko tudi smrtna bolezen. Povzroča jo okužba z bakterijo Mycobacterium tuberculosis. Zanjo je značilna nenavadna struktura celične ovojnice, ki je zgrajena iz ... mikolne kisline. Vse večji problem pri zdravljenju predstavlja odpornost M. tuberculosis proti antituberkulotikom, ki se uporabljajo v standardni terapiji. Izoniazid, zdravilna učinkovina prvega izbora, je predzdravilo. Za njegovo delovanje je potrebna in vivo aktivacija z encimom KatG. Nastali adukt je močan zaviralec encima InhA, ki je udeležen pri biosintezi mikolnih kislin. Ker prihaja pogosto do mutacij na encimu KatG, so zaviralci, katerih tarča je neposredno encim InhA, obetavni kandidati za razvoj novih zdravilnih učinkovin proti vse večji grožnji sevov M. tuberculosis, odpornih na zdravila. V okviru magistrske naloge smo sintetizirali štiri potencialne direktne zaviralce encima InhA (7, 8, 15 in 16). Izhajali smo iz spojine ?, kjer smo namesto tetrahidropiranskega dela uvedli 1,2,3,4-tetrahidropirolo[1,2-a]pirazin z različnimi substituenti na mestu 1 in 6 in tako raziskovali kemijski prostor v aktivnem mestu encima InhA, kjer se tvorijo lipofilne interakcije med učinkovino in vezavnim mestom. Sintetiziranim spojinam so na Fakulteti za farmacijo na Univerzi v Ljubljani določili IC50. Spojina 15 je izkazala največjo aktivnost, IC50 znaša 830 nM. Ker gre za molekulo s kiralnim centrom, bi bila v prihodnje smiselna kiralna ločba, saj predvidevamo, da je za aktivnost odgovoren le en enantiomer. V nadaljevanju smo ugotovili, da je potrebno na mestu 6 v 1,2,3,4-tetrahidropirolo[1,2a]pirazinu uvesti substituent zaradi drugače nestabilnega pirola. V drugem delu magistrske naloge smo izvedli kiralno ločbo racemne zmesi tiadiazolnega tipa zaviralca InhA M1155 in racemne zmesi zaviralca imunoproteasoma LR114P. Izvajali smo direktno kiralno ločevanje spojin s HPLC. Pri prvi spojini enantiomerov nismo uspeli ločiti na bazni liniji, vendar smo dobili zadovoljive rezultate za nadaljnje potrebe. Z optimizacijo pogojev ločbe druge spojine smo prišli do ločbe enantiomerov na bazni liniji. Zbrane posamezne frakcije enantiomerov bodo uporabili na Fakulteti za farmacijo za nadaljnja testiranja.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [A. Sinjur], 2019Language - slovenianCOBISS.SI-ID - 4719217
Author
Sinjur, Anja
Other authors
Pajk, Stane, 1983-
Topics
Tuberkuloza |
Kromatografija |
direktni zaviralci InhA |
kiralna kromatografija |
sinteza zaviralcev InhA
Library/institution |
City | Acronym | For loan | Other holdings |
---|---|---|---|---|
Faculty of Pharmacy, Ljubljana | Ljubljana | FFALJ |
reading room 1 cop.
|
Shelf entry
Permalink
- URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year | Impact factor | Edition | Category | Classification | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Select the library membership card:
If the library membership card is not in the list,
add a new one.
DRS, in which the journal is indexed
Database name | Field | Year |
---|
Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
---|---|
Sinjur, Anja | |
Pajk, Stane, 1983- | 28861 |
Source: Personal bibliographies
and: SICRIS
Select pickup location:
Material pickup by post
Delivery address:
Address is missing from the member's data.
The address retrieval service is currently unavailable, please try again.
By clicking the "OK" button, you will confirm the pickup location selected above and complete the reservation process.
By clicking the "OK" button, you will confirm the above pickup location and delivery address, and complete the reservation process.
By clicking the "OK" button, you will confirm the address selected above and complete the reservation process.
Notification
Automatic login and reservation service currently not available. You can reserve the material on the Biblos portal or try again here later.
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
Pickup location | Material status | Reservation |
---|
Reservation in progress
Please wait a moment.
Reservation was successful.
Reservation failed.
Reservation...
Membership card:
Pickup location: