Inhibition of nitric oxide synthase by antineoplastic anthracyclines.

Nitric oxide synthase, the enzyme responsible for the synthesis of nitric oxide and citrulline from arginine, was potently inhibited by the anthracycline antibiotics doxorubicin (Ki = 24 microM) and aclarubicin (Ki = 50 microM). These drugs were non-competitive inhibitors with respect to arginine. This action on nitric oxide synthase may explain some of the cardiovascular and cytotoxic actions of these chemotherapeutic drugs.