Naslov
Synthesis, X-ray crystal structure study and antitumoral evaluations of 5,6-disubstituted pyrimidine derivatives

Autori
Gazivoda Kraljević, Tatjana ; Krištafor, Svjetlana ; Šuman, Lidija ; Kralj, Marijeta ; Ametamey, Simon M. ; Cetina, Mario ; Raić-Malić, Silvana

Izvornik
Bioorganic & medicinal chemistry (0968-0896) 18 (2010), 7; 2704-2712

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

Ključne riječi
5, 6-disubstituted pyrimidines ; lithiation ; positron-emission tomography (PET) ; cytostatic evaluations ; X-ray diffraction ; hydrogen bonds ; pi•••pi interactions

Sažetak
5, 6-Disubstituted pyrimidine derivatives (3-20) were prepared by intramolecular cyclization reaction of alpha-(1carbamyliminomethylene)-gamma-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by 1H NMR, 13C NMR and mass spectra. Structures of compounds 4, 7 and 14 were unambiguously confirmed by X-ray crystal structural analysis. Supramolecular structures of these three compounds differ significantly. Two N-H•••O and one C-H•••O hydrogen bonds in 4 form three-dimensional network. One O-H•••N hydrogen bond and one pi•••pi interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only pi•••pi stacking interactions participate, so forming chains. The compounds were evaluated for their cytostatic activities against human malignant cell lines. Of all tested compounds, 2, 4-dimethoxy5-methoxytritylethylpyrimidine (9) and 2, 4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC50 = 0.4 µM).

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti

POVEZANOST RADA