Fluorocyclopentenyl-cytosine with Broad Spectrum and Potent Antitumor Activity

• Published in: Journal of medicinal chemistry Vol. 55; no. 9; pp. 4521 - 4525
• Main Authors: Choi, Won Jun, Chung, Hwa-Jin, Chandra, Girish, Alexander, Varughese, Zhao, Long Xuan, Lee, Hyuk Woo, Nayak, Akshata, Majik, Mahesh S, Kim, Hea Ok, Kim, Jin-Hee, Lee, Young B, Ahn, Chang H, Lee, Sang Kook, Jeong, Lak Shin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10-05-2012
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Cyclopentanes - chemical synthesis; Cyclopentanes - pharmacology; Cytosine - analogs & derivatives; Cytosine - pharmacology; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Mice; Mice, Nude; Xenograft Model Antitumor Assays
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm3004009

On the basis of the potent biological activity of cyclopentenyl-pyrimidines, fluorocyclopentenyl-pyrimidines were designed and synthesized from d-ribose. Among these, the cytosine derivative 5a showed highly potent antigrowth effects in a broad range of tumor cell lines and very potent antitumor activity in a nude mouse tumor xenograft model implanted with A549 human lung cancer cells. However, its 2′-deoxycytidine derivative 5b did not show any antigrowth effects, indicating that 2′-hydroxyl group is essential for the biological activity.