Park Yeon Hee, Choi Won Jun, Tipnis Amol S, Lee Kang Man, Jeong Lak Shin
Department of Bioinspired Science and Division of Life and Pharmaceutical Sciences, College of Pharmacy, Ewha Womans University, Seoul, Korea.
Nucleosides Nucleotides Nucleic Acids. 2009 May;28(5):601-13. doi: 10.1080/15257770903054316.
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.
基于截短的环戊烯基胞嘧啶对S-腺苷同型半胱氨酸水解酶（SAH）的抑制活性，以亲电氟化作为关键步骤，从D-核糖高效合成了其氟环戊烯基嘧啶衍生物。对最终的核苷进行了SAH抑制活性评估，其中尿嘧啶衍生物9表现出显著的抑制活性（IC(50)=8.53微摩尔）。还在几种人类癌细胞系如纤维肉瘤、胃癌、白血病和结肠癌中评估了它们的细胞毒性作用，但在高达100微摩尔的浓度下它们未显示出任何细胞毒性作用，这表明4'-羟甲基基团对于抗癌活性至关重要。
