Návrh a syntéza nových potenciálně cytotoxicky aktivních salicylamidů

Dušek, Jan

Publikace:
Návrh a syntéza nových potenciálně cytotoxicky aktivních salicylamidů

Disertační práceopen access

dc.contributor.author	Dušek, Jan
dc.contributor.referee	Jampílek, Josef
dc.contributor.referee	Krátký, Martin
dc.date.accepted	2020-06-29
dc.date.accessioned	2020-07-22T07:37:56Z
dc.date.available	2020-07-22T07:37:56Z
dc.date.issued	2020
dc.date.submitted	2020-05-28
dc.description.abstract	Byla provedena rozsahla literarni re.er.e zam..ena na metody syntezy a popsane biologicke aktivity salicylamid., na mo.nosti syntezy peptid. v.etn. pou.itych .inidel, aditiv a aspekt. racemizace substratu, a na molekuly schopne inhibice proteasomu. Bylo navr.eno a experimentaln. ov..eno n.kolik mo.nych p.istup. ke konstrukci salicylamid. s peptidovym .et.zcem, ktere navazuji a roz.i.uji sou.asne znalosti v teto oblasti. Byla vybrana nejvhodn.j.i synteticka metoda, ktera byla dale optimalizovana zejmena za u.elem omezeni racemizace. Byla provedena synteza serie slou.enin odvozenych od substituovane kyseliny salicylove a dipeptid., ktere byly vhodnym zp.sobem charakterizovany (1H a 13C NMR, I., HRMS v uspo.adani MALDI-TOF, CHN analyza). Dale bylo provedeno testovani jejich biologickych aktivit (antiproliferativni aktivita v..i kmen.m leukemie K562 a CEM a mnoho.etneho myelomu U266, proteasomalni inhibice U266 v.etn. selektivity v..i jednotlivym podjednotkam ?Ŕ kruhu proteasomu 20S U266 a .asovemuho pr.b.hu inhibice v r.znych koncentracich p.ipravenych salicylamid.).	cze
dc.description.abstract-translated	Extensive literary review describing biological activities and methods of salicylamide synthesis, describing peptide synthesis including used reagents, aditives and aspects of substrate racemization, and describing molecules able of proteasomal inhibition was carried out and is presented. Several synthetical strategies for salicylamide containing a peptide chain was designed and experimentaly verified. Proposed samlicylamides are extending current state of knowledge about said topic. The most suitable synthetic method was chosen and further optimized with the aim of resolve the peptide racemisation issue which occured during the synthesis. Series of salicylamides with peptide sidechain was synthesized and characterized (1H a 13C NMR, IR, HRMS in the MALDI-TOF setting, CHN analysis). Furthermore, prepared compounds were tested for their biological activities (antiproliferative activity against leukemia cell lines K562 and CEM and multiple myeloma cell line U266, proteasomal inhibition of U266 including the selectivity towards proteolytic subunits of â ring of 20S proteasome U266, time progress of proteasomal inhibition at various salicylamide concentration levels).	eng
dc.description.department	Fakulta chemicko-technologická	cze
dc.description.grade	Dokončená práce s úspěšnou obhajobou	cze
dc.identifier	Univerzitní knihovna (studovna)	cze
dc.identifier.signature	D40327
dc.identifier.stag	40634
dc.identifier.uri	https://hdl.handle.net/10195/75965
dc.language.iso	cze
dc.publisher	Univerzita Pardubice	cze
dc.rights	Bez omezení
dc.subject	alifatické salicylamidy	cze
dc.subject	inhibice proteasomu	cze
dc.subject	syntéza peptidů	cze
dc.subject	amidační činidla	cze
dc.subject	racemizace	cze
dc.subject	aliphatic salicylamides	eng
dc.subject	inhibition of proteasome	eng
dc.subject	peptide synthesis	eng
dc.subject	amidation reagents	eng
dc.subject	racemization	eng
dc.thesis.degree-discipline	Organická chemie	cze
dc.thesis.degree-grantor	Univerzita Pardubice. Fakulta chemicko-technologická	cze
dc.thesis.degree-name	Ph.D.
dc.thesis.degree-program	Organická chemie	cze
dc.title	Návrh a syntéza nových potenciálně cytotoxicky aktivních salicylamidů	cze
dc.title.alternative	Design and synthesis of novel potentially cytotoxically active salicylamides	eng
dc.type	disertační práce	cze
dspace.entity.type	Publication