dc.contributor.advisor | Bugarčić, Zorica | |
dc.contributor.other | Janković, Nenad | |
dc.contributor.other | Popsavin, Mirjana | |
dc.contributor.other | Ratković, Zoran | |
dc.contributor.other | Baskić, Dejan | |
dc.creator | Joksimović, Nenad | |
dc.date.accessioned | 2020-10-24T12:31:03Z | |
dc.date.available | 2020-10-24T12:31:03Z | |
dc.date.issued | 2020-07-15 | |
dc.identifier.uri | http://eteze.kg.ac.rs/application/showtheses?thesesId=7542 | |
dc.identifier.uri | https://fedorakg.kg.ac.rs/fedora/get/o:1258/bdef:Content/download | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/17539 | |
dc.description | Rezime:
U ovoj disertaciji sintetisana je serija acilpiruvata u visokim prinosima
reakcijom Klajzenove kondenzacije. Acilpiruvati su zatim korišćeni kao prekursori za
sintezu tri nove klase jedinjenja pod pretpostavkom da će pokazati bolja biološka
svojstva od samih acilpiruvata. Sintetisana je serija od dvadeset i pet novih 1,5-
diaril-4-(2-tienilkarbonil)-3-hidroksi-3-pirolin-2-oni. Pored toga, bilo je veoma
interesantno ispitati kako koordinacija za neke jone prelaznih metala utiče na
aktivnost organskih molekula kao što su acilpiruvati. Zbog toga je sintetisano
jedanaest novih metalo-organskih kompleksa sa acilpiruvatima kao ligandima koji
sadrže Cu2+ ili Pd2+ kao centralni jon metala. Sva novo-sintetisana jedinjenja su
okarakterisana spektroskopskom analizom (UV-Vis, IR, 1H i 13C NMR), masenom
spektrometrijom i elementalnom analizom. Rendgenska strukturna analiza je takođe
urađena gde je to bilo moguće.
Novosintetizovani molekuli testirani su na antioksidativni, antimikrobni i
antitumorski potencijal. DPPH test pirolidinona je pokazao da ova jedinjenja poseduju
dobru antioksidativnu aktivnost (najniža IC50 vrednost iznosi 166,75 µg/ml). Ovaj test
je takođe pokazao da većina acilpiruvata poseduje bolju antioksidativnu aktivnost od
odgovarajućih metalo-organskih jedinjenja bakra(II).
Ispitivanja antimikrobne aktivnosti su otkrila da pirolidinoni pokazuju
značajnu inhibitorsku aktivnost na soju bakterija Staphylococcus aureus u prilično
niskim koncentracijama (najniža izmerena MIC vrednost iznosi 0,312 mg/ml), dok je
najosetljiviji soj gljivica bio Trichophyton mentagrophytes sa najnižom MIC od 0,625
mg/ml. MIC vrednosti za metalo-organska jedinjenje bakra(II) na testiranim
mikroorganizmima bile su u rasponu od 0,048 do 3,125 mg/ml. Najosetljiviji soj
bakterija bio je Proteus mirabilis, dok je među gljivicama najosetljiviji soj bio Candida
albicans. | sr |
dc.description | SUMMARY:
In this dissertation a series of acylpyruvates in high yields has been synthesized using the
Claisen condensation reaction, which were then used as precursors for the synthesis of three new
classes of compounds. Three new classes of compounds were synthesized under the assumption
that they would show better biological properties than the acylpyruvates themselves. A series of
twenty-five novel and one previously published 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-
pyrrolin-2-ones were synthesized. In addition, it was very interesting to examine how
coordination for some metal ion affects the activity of organic molecules such as acylpyruvates,
and therefore eleven new metal-organic complexes were synthesized with acylpyruvates as
ligands containing Cu2+ or Pd2+ as the central metal ion. All newly synthesized compounds were
characterized by spectroscopic analysis (UV-Vis, IR, 1H and 13C NMR), mass spectrometry and
elemental analysis. X-ray structural analysis was also performed where possible.
The newly synthesized molecules were tested for antioxidant, antimicrobial and
antitumor potential. The DPPH test showed that most acylpyruvates showed better antioxidant
activity than the corresponding metal-organic copper(II) compounds. MIC values for the metalorganic copper(II) compounds on the tested microorganisms were in range from 0.048 to 3.125
mg/ml. The most sensitive bacteria strain was Proteus mirabilis, while among the fungi the most
sensitive strain was Candida albicans. The results of the antitumor activity showed that these
compounds showed good cytotoxic activity. All metal-organic copper(II) compounds showed
lower IC50 values on the LS174 and A549 cell lines compared to cisplatin.
The results of the antitumor potential for palladium(II) metal-organic complexes showed
that the three compounds had very good cytotoxic activity on HeLa cells and significant activity
on MDA-MB 231 cells. The results obtained by examining the interations between the palladium
compound and cisplatin indicate that these compounds may be useful as adjuvants in therapy for
the treatment of tumors, reducing the doses of cisplatin and thus the side effects of this drug. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Крагујевцу, Природно-математички факултет | sr |
dc.relation | info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172011/RS// | |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | Универзитет у Крагујевцу | sr |
dc.title | Acilpiruvati kao prekursori u sintezi nekih biološki aktivnih jedinjenja | sr |
dc.type | doctoralThesis | en |
dc.rights.license | BY-NC-ND | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/66155/Disertacija.pdf | |
dc.identifier.fulltext | https://nardus.mpn.gov.rs/bitstream/id/66156/Izvestaj_Nenad_Joksimovic_PMF.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_17539 | |