ELECTROCHEMICAL AND ENZYMATIC STUDY OF 2-CHLORO-2'-DEOXYADENOSINE (ANTILEUKEMIC AGENT) AND RELATED-COMPOUNDS

The electrochemical reduction of two 2-halogeno derivatives of 2'-deox yadenosine, antileukemic agents (2-chloro-2'-deoxyadenosine (2-CldAdo) and 2-bromo-2'-deoxyadenosine (2-BrdAdo)) and related ribosides (7-me thyladenosine (m(7)Ado) and purine riboside (PR)) have been examined b y d.c. and a.c. polarography as well as by macroelectrolysis. 2-CldAdo (Cladribine, Leustatin) undergoes a one-step reduction in very acidic medium, pH 1-3, while the reduction of 2-BrdAdo occurs in two steps i n the pH range 1-6. Both 2-halogeno adenosines involve reduction of th e C-halogen bond and the pyrimidine ring. The reduction products have been examined by UV and nuclear magnetic resonance spectroscopy and hi gh performance liquid chromatography analysis and the reduction mechan ism has been formulated. All investigated compounds including PR and m (7)Ado exhibit high surface activity confirmed by a.c. polarography. A ll investigated compounds and theirs reduction products were tested fo r inhibitory activity vs. Escherichia coli PNP with inosine as substra te and inhibition constants have been determined. 2-CldAdo and 2-BrdAd o, as well as the reduction products of 2-CldAdo and PR, were found to be good inhibitors of E. coli PNP, whereas the reduction products of m(7)Ado and 2'-deoxyadenosine do not bind to the enzyme.