izpis_h1_title_alt

Sinteza piridinostilbenskih zaviralcev ligaz Mur
Verbič, Klara (Author), Hrast, Martina (Mentor) More about this mentor... This link opens in a new window, Knez, Damijan (Co-mentor)

.pdfPDF - Presentation file, Download (1,79 MB)
MD5: 8D3EE2EBDB7F81D766F9EB5ED3018621

Abstract
Odpornost bakterij na protibakterijske učinkovine postaja vse večji zdravstveni problem. Glavna razloga za to sta neustrezna uporaba protibakterijskih učinkovin in upočasnjen razvoj novih protibakterijskih učinkovin. Zaradi tega sta potrebna razvoj in sinteza novih protibakterijskih učinkovin. V raziskavah se je pokazalo, da predstavljajo encimi, ki sodelujejo v znotrajceličnih stopnjah biosinteze peptidoglikana, velik potencial za razvoj novih učinkovin. V magistrski nalogi smo raziskovali sinteze novih piridinostilbenskih zaviralcev od ATP odvisnih ligaz MurC–F, ki katalizirajo pripajanje peptidov na peptidno verigo prekurzorja peptidoglikana. Zaviralce smo načrtovali na osnovi strukture že znanega zaviralca, ki so ga pri testiranju knjižnice protein kinaznih zaviralcev na ligaze Mur odkrili raziskovalci na Fakulteti za farmacijo. Najprej smo zamenjali furanski obroč z različnimi aromatskimi fragmenti in sintetizirali pet novih zaviralcev MurC–F. Nato smo spremenili tetrazolni del molekule in pripravili še dva dodatna zaviralca MurC–F. Z zamenjavo furanskega fragmenta smo dobili zaviralec encimov MurC–F, ki je imel podobno delovanje kot izhodna spojina (spojina 4b). Tudi spojini 5 in 6, ki sta imeli spremenjen tetrazolni del, sta se izkazali kot dobra zaviralca ligaz MurC-F. Sintetizirane spojine so dobro izhodišče za nadaljnje sinteze in načrtovanje novih multiplih zaviralcev ligaz MurC-F.

Language:Slovenian
Keywords:protibakterijske učinkovine, piridinostilbenski zaviralci, MurC–F
Work type:Master's thesis/paper (mb22)
Organization:FFA - Faculty of Pharmacy
Year:2019
Views:566
Downloads:280
Metadata:XML RDF-CHPDL DC-XML DC-RDF
 
Average score:(0 votes)
Your score:Voting is allowed only to logged in users.
:
Share:AddThis
AddThis uses cookies that require your consent. Edit consent...

Secondary language

Language:English
Title:Synthesis of pyridinostilbene inhibitors of Mur ligases
Abstract:
The bacterial resistance to antibiotics is becoming an increasing health problem. The main reasons are inappropriate use of antibiotics and the decreasing number of novel antibiotics. For this reason, the development and synthesis of new antibacterial agents is required. Studies have shown that enzymes involved in intracellular levels of peptidoglycan biosynthesis have a great potential for the development of new antibacterial agents. In our work we synthesized new pyridinostylbene inhibitors of ATP dependent MurC–F ligases, which catalyses the addition of peptides to peptidoglycan precursor. A new series of inhibitors was designed and synthesized, based on the structure of the known inhibitor, which was identified in the screening of the library of protein kinase inhibitors against Mur ligases at the Faculty of Pharmacy. First, we replaced the furan ring with various aromatic fragments and synthesized five new MurC–F inhibitors. Additionally, the tetrazole moiety of the molecule was changed, and two additional MurC–F inhibitors were synthesized. By replacing the furan fragment, a MurC–F enzyme inhibitor was obtained which had similar activity to the starting compound (compound 4b). Pyridinostylbene derivatives with altered tetrazole moiety 5 and 6 were also proven to be good inhibitors. Synthesized derivatives provide a good starting point for further synthesis and design of multiple inhibitors of the MurC-F ligases.

Keywords:antibacterial agents, pyridinostilbene inhibitors, MurC–F

Similar documents

Similar works from RUL:
Similar works from other Slovenian collections:

Comments

Leave comment

You have to log in to leave a comment.

Comments (0)
0 - 0 / 0
 
There are no comments!

Back