Synthesis and biological activity of some 8-substituted selenoguanosine cyclic 3',5'-phosphates and related compounds.
8-Bromoguanosine cyclic 3',5'-monophosphate, 8-bromoguanosine 5'-monophosphate, and 8-bromoguanosine served as intermediates for the chemical synthesis of a series of 8-substituted seleno cyclic nucleotides, nucleotides, and their nucleosides. Selenourea was found to be a useful reagent in synthesizing these seleno-substituted nucleoside, nucleotide, and cyclic nucleotide. A nucleic acid analyzer was used to study the hydrolysis of these cyclic nucleotides by phosphodiesterase. It was found that all of the 8-substituted selenoguanosine cyclic 3',5'-phosphates synthesized, except 8-MeSe-cGMP, were resistant to hydrolyze by phosphodiesterase. These 8-substituted seleno cyclic GMP derivatives showed some antitumor activities against murine leukemic cells (L5178Y) in vitro and in vivo.
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000818:Animals; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006150:Guanine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006868:Hydrolysis; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D009712:Nucleotides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D012643:Selenium / Q000494:pharmacology / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet
D006150:Guanine Nucleotides; D009712:Nucleotides, Cyclic; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP; D012643:Selenium