Truncated fluorocyclopentenyl pyrimidines as S-adenosylhomocysteine hydrolase inhibitors
Yeon Hee Park1, Won Jun Choi, Amol S Tipnis
1Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
Abstract:
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.
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