| Abstract | Boronične kiseline su spojevi u kojima je trovalentni borov atom povezan s jednom alkilnom ili arilnom
skupinom te dvije hidroksilne skupine. Zanimljive su za istraživanje zbog malih molekulskih masa, termičke
stabilnosti, niske toksičnosti, blage kiselosti te inertnosti u doticaju s vodom i kisikom. Djeluju kao izvrsni
reaktanti, ali pokazuju i jaku bioaktivnost, što im je posljednjih godina priskrbilo podosta pozornosti. Boronične
kiseline stvaraju nekoliko derivata, čija su svojstva, unatoč povećanom interesu, do danas još razmjerno
neistražena.
U okviru ove doktorske disertacije provedeno je prvo opsežno usporedno istraživanje bioloških učinaka
odabranih boroničnih kiselina i njihovih derivata: fenilboronične kiseline, 2,4,6-trifluorofenil boronične kiseline,
trimetil boroksina, trimetoksi boroksina i dikalijevogtrioksohidroksitetrafluortriborata, te validacija njihovog
inhibitornog djelovanja na izdvojene enzime: butirilkolinesterazu, tirozinazu, heksokinazu, laktat-dehidrogenazu
i piruvat-kinazu. Citotoksični i antitumorski učinci ispitani su na tumorskim staničnim kulturama 4Tl mišjeg
adenokarcinoma dojke, BI 6F I O mišjeg melanoma i SCCVIT mišjeg karcinoma pločastih stanica kože. Svi
ispitivani spojevi, s izuzetkom 2,4,6-trifluorofenil boronične kiseline, uzrokovali su značajno smanjenje
vijabilnosti tumorskih stanica u in vitro testovima, dok su u in vivo uvjetima znatno usporili njihov rast. U
istraživanjima inhibitornog djelovanja, bolje učinke polučili su derivati s boroksinskim prstenom, posebice
dikalijevtrioksohidroksitetrafluortriborat i trimetoksi boroksin, u odnosu na ispitivane boronične kiseline.
Antioksidacijska aktivnost ispitana je prin*nom tri različite spektrofotometrijske metode, pri čemu su svi
ispitivani spojevi pokazali zanemarivu djelotvornost.
Ostvareni rezultati upućuju na zaključak kako kod ispitivanih boroničnih kiselina i njihovih derivata postoji
izvjesni biomedicinski potencijal te predstavljaju temelj za daljnja istraživanja. |
| Abstract (english) | Boronic acids are compounds in which trivalent boron atom is connected with one alkyl or arly and two hydroxil
groups. They are interesting due to their low molecular masses, their thermal stability, low toxicity, mild acidity
and inertness to water and oxygen. The fact that they act as excellent reactants and exhibit strong bioactivity
brought them a great deal of attention in recent years. Boronic acids form several derivates which, despite
growing interest, still remain relatively unexplored.
This doctoral thesis represents the first comprehensive comparative study carried out to elucidate the biological
effects of selected boronic acids and their derivates: phenyboronic acid, 2,4,6-tritluorophenyl boronic acid,
trimethylboroxine, trimethoxyboroxine and dipottasium trioxohydroxytetraflourotriborate, and to assess their
inhibitory activity on isolated enzymes: butyrylcholinesterase, tyrosinase, hexokinase, lactate dehydrogenase and
pyruvate kinase. Cytotoxic and anti tumor effects were examined using 4Tl mammary carcinoma, BI 6F I O
mouse melanoma and SCCVII squamous cell carcinoma cell lines. With exception of 2,4,6-trifluorophenyl
boronic acid, ali selected compounds have significantly reduced the tumor cell viability in vitro, and have greatly
slowed their growth in vivo. When it comes to the inhibitory effects, better results were yielded by derivates with
the boroxine ring - particulary, dipottasium t:rioxohydroxytetraflourotriborate and trimethoxyboroxine - in
comparison to the selected boronic acids. Antioxidant activity was studied using three different
spectrophotomelric methods where ali ofthe selected compounds demonstrated negliable effectivness.
Considering the results, it may be suggested that selected boronic acids and their derivates posses ce11ain
biomedical potential that should be thouroughly investigated. |
