ANTIINFLAMMATORY AND ANTI-OSTEOPOROTIC ACTIVITIES OF BASE-BORONATED NUCLEOSIDES AND PHOSPHATE-BORONATED NUCLEOTIDES IN RODENTS

The 2'-deoxyribonucleoside cyanoboranes were effective anti-inflammato ry agents in rodents at 2-8 mg/kg; they blocked induced edema, septic shock, and pleurisy. Overall compounds 3',5'-O-(bis(triisopropylsilyl) -2'-deoxyinosine (1), 3',5'-O-bis(triisopropylsilyl)-2'-deoxycytidine (10), N-3-(cyanoboryl)-2'-deoxycytidine (11), N-7-(cyanoboryl)-N-2-iso butyryl-3',5'-O- bis(triisopropylsilyl)-2'-deoxyguanosine (20), and xy trityl)3'-O-(triisopropylsilyl)2'-deoxyguanosine (22) were the most ac tive when all of the anti-inflammatory screens are considered. The age nts also blocked both local and central pain caused by inflammation. T hese nucleosides blocked calcium resorption but were less effective co mpared to other amine carboxyboranes. The inflammation process appeare d blocked by these compounds because of their effectiveness in reducin g both hydrolytic lysosomal enzyme and proteolytic enzyme activities. The agents were also dual inhibitors of prostaglandin cyclooxygenase a nd 5'-lipoxygenase activities in leukocytes and macrophages. These age nts at 10(-4) M demonstrated no specific organ toxicity to ileum mucos a cells grown in tissue culture.