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Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity


Noll, Steffi; Kralj, Marijeta; Šuman, Lidija; Stephan, Holger; Piantanida, Ivo
Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity // European journal of medicinal chemistry, 44 (2009), 3; 1172-1179 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis of modified pyrimidine bases and positive impact of chemically reactive substituents on their in vitro antiproliferative activity

Autori
Noll, Steffi ; Kralj, Marijeta ; Šuman, Lidija ; Stephan, Holger ; Piantanida, Ivo

Izvornik
European journal of medicinal chemistry (0223-5234) 44 (2009), 3; 1172-1179

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

Ključne riječi
Modified pyrimidine bases; antiproliferative activity; human tumor cell lines

Sažetak
The antiproliferative activity screening on human tumor cell lines of a series of modified uracil and cytosine bases as well as some corresponding acyclonucleotides, and comparison of structure-activity relationship revealed the importance of chemical reactivity of the substituent attached to the C5-position of uracil for the activity of studied compounds. Namely, the results obtained for the most active compounds, 5-(Chloroacetylamino)uracil (2) and its acyclic sugar analogue 18, suggest that formation of a covalent bond between reactive substitutent and several possible targets within the thymidylate synthase mechanism (sulphur of the cysteine residue, basic part of the enzyme, N, N-methylene tetrahydrofolate or its reactive iminium forms) is the most probable mode of action. In addition, novel C5-substitued uracil derivative 6 (5-[bis-(2-p-methoxybenzylthioethyl)amine]acetylamino-uracil) exhibited high antiproliferative activity against HeLa and MiaPaCa-2 cell lines, by an as yet unknown mechanism.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
098-0982464-2514 - Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA (Marijeta Kralj, )
098-0982914-2918 - Dizajn, sinteza i ispitivanje interakcija malih molekula s DNA, RNA i proteinima (Ivo Piantanida, )

Ustanove
Institut "Ruđer Bošković", Zagreb

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