Synthesis of Novel Nucleoside Analogue Phosphorothioamidate Prodrugs and in vitro Anticancer Evaluation Against RKO Human Colon Carcinoma Cells |
| |
| Authors: | Wei Liu Lin Zhang Honggang Zhou Cheng Yang Zhiwei Miao Yufen Zhao |
| |
| Institution: | 1. College of Sciences , Tianjin University of Science and Technology , Tianjin , China;2. High Throughput Molecular Drug Discovery Center , Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin , China;3. High Throughput Molecular Drug Discovery Center , Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin , China;4. High Throughput Molecular Drug Discovery Center , Tianjin International Joint Academy of Biotechnology and Medicine , Tianjin , China;5. College of Pharmacy , NanKai University , Tianjin , China;6. College of Pharmacy , NanKai University , Tianjin , China |
| |
| Abstract: | Novel phosphorothioamidates of pyrimidine nucleoside analogues have been prepared and evaluated in vitro against RKO human colon cancer cell by the MTT cytotoxicity assay. The parent nucleoside analogues were inactive in this assay, while the phosphorothioamidate prodrugs were active at low uM levels in some cases. The O-isopropyl phosphorothioamidate of 2 ′,3 ′-O-isopropylidene-uridine containing the L-phenylalanine ethyl ester 6f was the most active at 148 uM, a 10-fold enhancement in anticancer activity compared with the parent nucleoside 2 with no increase in cytotoxicity. |
| |
| Keywords: | Phosphorothioamidate prodrug nucleoside anticancer activity colon cancer |
|
|
