Naslov
Synthesis and in vitro antiproliferative activity of N-sulfonyl and sulfonamido nucleobase derivatives

Autori
Žinić, Biserka ; Ismaili, Hamit ; Hoti, Ramiz ; Suver Stević, Mirjana ; Glavaš-Obrovac, Ljubica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
ESOC 2011 - 17th European Symposium on Organic Chemistry, Crete, Greece / - , 2011

Skup
ESOC 2011 - 17th European Symposium on Organic Chemistry, Crete, Greece

Mjesto i datum
Grčka, 10.07.2011. - 15.07.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
C-5 sulfonamido-pyrimidines; N-9-sulfonylpurines; C-6 sulfonamido-purines; in vitro antiproliferative activity

Sažetak
Recently, we have prepared a series of novel N-1 sulfonyl pyrimidine derivatives which exhibit strong antitumor activity.1-3 As a part of our program directed toward the synthesis and characterization of biologically active nucleobase derivatives, we decided to synthesized N-sulfonyl and sulfonamido derivatives of purine and pyrimidine nucleobases. The sulfonylation of amines with sulfonyl chlorides in the presence of a base is still being used as the method of choice because of high efficiency and simplicity of the reaction. The series of C-5 sulfonamido pyrimidines I were prepared by heating 5-aminouracil with the selected sulfonyl chlorides in pyridine. The reaction was regioselective and only isolated products were the C-5 substituted pyrimidines. We found that the sulfonylation reaction of 6-chloropurine and guanine with the selected sulfonyl chlorides in the presence of potassium hydroxide was regioselective at lower temperature and isolated products were N-9-sulfonyl derivatives II and IV. On the other hand, the reaction of 6-chloropurine with different sulfonamides activated with potassium carbonate afforded C-6 sulfonamido derivatives III. The cytotoxicity of compounds were tested against normal cells (MDCK1) and human leukemia (Raji, K562, Jurkat) and lymphoma (HuT78) cell lines by the MTT assay. Depending on the dose applied compounds showed moderate to high antiproliferative activity against a panel of haematological malignancies in vitro.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA