Truncated fluorocyclopentenyl pyrimidines as S-adenosylhomocysteine hydrolase inhibitors.
On the basis of inhibitory activity of truncated cyclopentenyl cytosine against S-adenosylhomocysteine hydrolase (SAH), its fluorocyclopentenyl pyrimidine derivatives were efficiently synthesized from D-ribose via electrophilic fluorination as a key step. The final nucleosides were evaluated for SAH inhibitory activity, among which the uracil derivative 9 showed significant inhibitory activity (IC(50) = 8.53 microM). They were also evaluated for cytotoxic effects in several human cancer cell lines such as fibro sarcoma, stomach cancer, leukemia, and colon cancer, but they did not show any cytotoxic effects up to 100 microM, indicating that 4'-hydroxymethyl groups are essential for the anticancer activity.
Park
Yeon Hee
YH
Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
Choi
Won Jun
WJ
Tipnis
Amol S
AS
Lee
Kang Man
KM
Jeong
Lak Shin
LS
D043383:Adenosylhomocysteinase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D017611:Fluorine Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D017611:Fluorine Compounds; D011743:Pyrimidines; D043383:Adenosylhomocysteinase