Antitumor activity of 2,2'-bipyridyl-6-carbothioamide: a ribonucleotide reductase inhibitor.
1. 2,2'-Bipyridyl-6-carbothioamide (BPYTA) is a synthesized compound with chelating properties demonstrating in vitro and in vivo antitumor activity. 2. The BPYTA cytotoxic effect is mainly due to the inhibition of ribonucleotide reductase (RR), a key enzyme in proliferating cells. The active form of BPYTA is its iron chelate [BPYTA-Fe(II), molar ratio 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 target. 4. BPYTA potently synergizes in vitro with hydroxyurea, the most widely used R2 inhibitor.
Nocentini
G
G
Department of Clinical Medicine, Pathology and Pharmacology, University of Perugia, Italy. FARMACO@TESEO.UNIPG.IT
Barzi
A
A
D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D015082:2,2'-Dipyridyl; C033291:2,2'-bipyridyl-6-carbothioamide; D012264:Ribonucleotide Reductases