ANTITUMOR-ACTIVITY OF 2,2'-BIPYRIDYL 6-CARBOTHIOAMIDE - A RIBONUCLEOTIDE REDUCTASE INHIBITOR

1. 2,2'-Bipyridyl-6-carbothioamide (BPYTA) is a synthesized compound w ith chelating properties demonstrating in vitro and in vivo antitumor activity. 2. The BPYTA cytotoxic effect is mainly due to the inhibitio n of ribonucleotide reductase (RR), a key enzyme in proliferating cell s. The active form of BPYTA is its iron chelate [BPYTA-Fe(II), molar r atio 2:1], which destroys the tyrosyl radical of RR small subunit (R2) . 3. The copper chelate of BPYTA [BPYTA-Cu(II), molar ratio 2:1] also has antiproliferative activity, but RR is not the only intracellular t arget. 4. BPYTA potently synergizes in vitro with hydroxyurea, the mos t widely used R2 inhibitor. (C) 1997 Elsevier Science Inc.