INHIBITOR OF NO-DEPENDENT ACTIVATION OF GUANYLATE CYCLASE SOLUBLE FORM Russian patent published in 2002 - IPC

FIELD: organic chemistry, biochemistry, enzymology. SUBSTANCE: invention relates to the use of the known antibiotic bruneomycin (streptonigrin, i. e. 5-amino-6-(7- -amino-5,8-dihydro-6-methoxy-5,8- dioxoquinoline-2-yl)-4-(2-hydroxy- -3,4-dimethoxyphenyl)-3-methylpyridine-2-carboxylic acid) and its known derivatives of the general formula (I) where if means a simple bond then X=NH and R= = 0 or =NH; if means a double bond then X means N and R means carboxyl-group, (lower alkyl)oxycarbonyl-group, [bis-(lower alkyl)amino]-ethoxycarbonylgroup or a group of the general formula C(O)NH-R¹ where R¹ means H, NH₂, NHC(O)-NH₂, NHC(S)-NH₂, unsubstituted lower alkyl, lower alkyl containing hydroxyl, carboxyl or (lower alkyl)oxycarbonyl group as a substitute or β-D-hexapyranozyl and their biochemically acceptable salts as an inhibitor of NO-dependent activation of a guanylate cyclase soluble form. The invention can be used in biochemistry for investigation of regulatory effects of nitrogen oxide and mechanism of action of a guanylate cyclase soluble form. Bruneomycin and its derivatives of the general formula (I) in concentration 1-100 mcM show an inhibitory effect on NO-dependent activation of a guanylate cyclase soluble form from human platelets caused by sodium nitroprusside. The concentration of bruneomycin at which activated effect of sodium nitroprusside is decreased by 50% (IC₅₀) is determined to be 4.2 mcM. The most related structural analogue is a doxorubicin in concentration 10 mcM inhibited activation of a guanylate cyclase soluble form by 26%. EFFECT: enhanced effectiveness of inhibitor, valuable biochemical properties. 2 cl