Discovery of a new template for anticancer agents: 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl-cytosine (2'-F-4'-seleno-ara-C).
The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).
Jeong
Lak Shin
LS
Department of Bioinspired Science, Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea. lakjeong@ewha.ac.kr
Tosh
Dilip K
DK
Choi
Won Jun
WJ
Lee
Sang Kook
SK
Kang
You-Jin
YJ
Choi
Sun
S
Lee
Jin Hee
JH
Lee
Hankil
H
Lee
Hyuk Woo
HW
Kim
Hea Ok
HO
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003596:Cytosine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D054879:Halogenation; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
C543822:2'-deoxy-2'-fluoro-4'-selenoarabinofuranosylcytosine; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D003561:Cytarabine; D003596:Cytosine