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Pregled bibliografske jedinice broj: 486543

Syntheses and Antitumor Evaluation of C(6) Isobutyl and Isobutenyl Substituted Pyrimidines and Dihydropyrrolo[1, 2-c]pyrimidin-1, 3-diones


Krištafor, Svjetlana; Gazivoda Kraljević, Tatjana; Ametamey, Simon M.; Cetina, Mario; Ratkaj, Ivana; Tandara Haček, Romana; Kraljević Pavelić, Sandra; Raić-Malić, Silvana
Syntheses and Antitumor Evaluation of C(6) Isobutyl and Isobutenyl Substituted Pyrimidines and Dihydropyrrolo[1, 2-c]pyrimidin-1, 3-diones // Chemistry & biodiversity, 8 (2011), 8; 1455-1469 doi:10.1002/cbdv.201000202 (međunarodna recenzija, članak, znanstveni)


Naslov
Syntheses and Antitumor Evaluation of C(6) Isobutyl and Isobutenyl Substituted Pyrimidines and Dihydropyrrolo[1, 2-c]pyrimidin-1, 3-diones

Autori
Krištafor, Svjetlana ; Gazivoda Kraljević, Tatjana ; Ametamey, Simon M. ; Cetina, Mario ; Ratkaj, Ivana ; Tandara Haček, Romana ; Kraljević Pavelić, Sandra ; Raić-Malić, Silvana

Izvornik
Chemistry & biodiversity (1612-1872) 8 (2011), 8; 1455-1469

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
C-6 isobutyl and isobutenyl substituted pyrimidine derivatives; cytostatic evaluation; apoptosis; X-ray crystal structure analysis

Sažetak
A growing body of evidence supports that pyrimidine derivatives, in which the sugar residues have been replaced by acyclic side chains, might be developed as promising anticancer agents that interfere with tumor cell proliferation, survival, and metastatic formation. In this work, we prepared novel pyrimidines bearing i-Bu (i.e., 3, 4, and 7–9) and isobutenyl (i.e., 5 and 10) side chains at C(6) and examined their in vitro effects on tumor cell lines. The dihydropyrrolo[1, 2-c]pyrimidin-1, 3-diones 6 and 11 were obtained as products of intramolecular cyclization, which occurred during the removal of Bn in 5 or MeO protecting groups in 10. Fluorination of 3 with diethylaminosulfur trifluoride (DAST) and then dehydrohalogenation of the resulting fluorinated derivative 4 afforded 6-isobut-2’-enyl pyrimidine derivative 5 with a C(2’)¼C(3’) bond. For the preparation of 6-isobut-1’-en-1-yl pyrimidine 10, a synthetic strategy involving acetylation of the 1, 3-diols was applied. Antitumor evaluation of compounds 3–11 showed that 2, 4-dimethoxypyrimidine containing 6-[(1, 3-dibenzyloxy)-2-hydroxy]methyl side chain, 3, exerted a strong antiproliferative effect on the studied tumor cell lines. Additionally, it was shown that the mechanism of antiproliferative effect of 3 in HeLa cells include early G2/M arrest and apoptosis, as well as a p53-independent S-phase arrest upon prolonged treatment.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
119-1193079-3069 - Novi organski i koordinacijski spojevi - sinteza i suodnos struktura-svojstvo (Branko Kaitner, )
125-0982464-2925 - Razvoj i primjena novih molekula u pozitron-emisijskoj tomografiji (PET) (Silvana Raić-Malić, )
335-0000000-3532 - Uloga IGF2 i signalni putovi nizvodno u karcinomima pluća čovjeka (Sandra Kraljević Pavelić, )
335-0982464-2393 - Molekularna obilježja miofibroblasta Dupuytrenove bolesti (Krešimir Pavelić, )

Ustanove
Tekstilno-tehnološki fakultet, Zagreb,
Prirodoslovno-matematički fakultet, Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Sveučilište u Rijeci - Odjel za biotehnologiju

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • CA Search (Chemical Abstracts)
  • MEDLINE


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