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Pregled bibliografske jedinice broj: 847310

Novel pyrimidine-2, 4-dione-1, 2, 3-triazole and furo[2, 3-d]pyrimidine-2-one-1, 2, 3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation


Gregorić, Tomislav; Sedić, Mirela; Grbčić, Petra; Tomljenović Paravić, Andrea; Kraljević Pavelić, Sandra; Cetina, Mario; Vianello, Robert; Raić-Malić, Silvana
Novel pyrimidine-2, 4-dione-1, 2, 3-triazole and furo[2, 3-d]pyrimidine-2-one-1, 2, 3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation // European journal of medicinal chemistry, 125 (2017), 1247-1267 doi:10.1016/j.ejmech.2016.11.028 (međunarodna recenzija, članak, znanstveni)


Naslov
Novel pyrimidine-2, 4-dione-1, 2, 3-triazole and furo[2, 3-d]pyrimidine-2-one-1, 2, 3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation
(Novel pyrimidine-2, 4-dione-1, 2, 3-triazole and furo[2, 3-d]pyrimidine-2-one-1, 2, 3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluationand X-ray analysis and biological evaluation)

Autori
Gregorić, Tomislav ; Sedić, Mirela ; Grbčić, Petra ; Tomljenović Paravić, Andrea ; Kraljević Pavelić, Sandra ; Cetina, Mario ; Vianello, Robert ; Raić-Malić, Silvana

Izvornik
European journal of medicinal chemistry (0223-5234) 125 (2017); 1247-1267

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

Ključne riječi
Furo[2 ; 3-d]pyrimidine-2-one ; 5-endo-trig cyclization ; Computational chemistry ; X-ray analysis ; Sphingolipid signaling ; Wee-1 kinase

Sažetak
Regioselective 1, 4-disubstituted 1, 2, 3-triazole tethered pyrimidine-2, 4-dione derivatives (5-23) were successfully prepared by the copper(I)- catalyzed click chemistry. While known palladium/copper cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2, 3-d]pyrimidine-2-one-1, 2, 3- triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses. The nature of substituents on alkynes and thereof homocoupled 1, 3-diynes predominantly influenced the ratio of the formed products in both pathways. In vitro antiproliferative activity of prepared compounds evaluated on five human cancer cell lines revealed that N, N-1, 3-bis-(1, 2, 3-triazole)-5- bromouracil (5-7) and 5, 6-disubstituted furo[2, 3- d]pyrimidine-2-one-1, 2, 3-triazole 34a hybrids exhibited the most pronounced cytostatic acitivities against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cells with higher potencies than the reference drug 5- fluorouracil. Cytostatic effect of pyrimidine-2, 4-dione-1, 2, 3-triazole hybrid 7 in HepG2 cells could be attributed to the Wee-1 kinase inhibition and abolishment of sphingolipid signaling mediated by acid ceramidase and sphingosine kinase 1. Importantly, this compound proved to be a nonmitochondrial toxicant, which makes it a promising candidate for further lead optimization and development of a new and more efficient agent for the treatment of hepatocellular carcinoma.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2013-11-5596 - SINTEZA I CITOSTATSKA ISPITIVANJA BIBLIOTEKE NOVIH DUŠIKOVIH HETEROCIKLA (Silvana Raić-Malić, )
HRZZ-IP-2014-09-3386 - Dizajn i sinteza novih dušikovih heterocikličkih fluorofora i fluorescentnih nanomaterijala kao kemijskih senzora za pH i metalne ione (Robert Vianello, )

Ustanove
Institut "Ruđer Bošković", Zagreb,
Tekstilno-tehnološki 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:


  • BIOSIS Previews (Biological Abstracts)
  • CA Search (Chemical Abstracts)
  • Education Research Abstracts Online
  • MEDLINE


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