Synthesis and biological activity evaluation of cytidine-5'-deoxy-5-fluoro-N-[(alkoxy/aryloxy)] carbonyl-cyclic 2',3'-carbonates.
Capecitabine, an oral prodrug of 5-FU was developed to improve the tumor selectivity and tolerability. To enhance the efficacy of capacitabine, a series of 5'-deoxy-5-fluorocytidine derivatives 5a-e were synthesized. In the present study, we investigated antitumor activity of 5'-deoxy-5-fluorocytidine derivatives both in vivo and in vitro methods. Title compounds were non-mutagenic to Salmonella typhimurium tester strain in Ames test. Compounds 5d and 5e are potent to inhibit the proliferation of NCI-69, PZ-HPV-7, MCF-7 and HeLa cells in MTT assay. In particular, 5d and 5e showed potent antitumor activities against L1210 leukemia cell line. Collectively, these findings suggest that 5d and 5e are more potent anti-cancer compounds than capecitabine.
Department of Chemistry, Sri Venkateswara University, Tirupati 517 502, India.
V
V
Jhansi Rani
A
A
Raghavendra
P
P
Kishore
Y
Y
Nanda Kumar
K
K
Hema Kumar
K
K
Jagadeeswarareddy
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000069287:Capecitabine; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D015195:Drug Design; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil