Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

Abstract Ribonucleotide reductase (RR) is an important therapeutic target for anticancer drugs. The structure of human RR features a 1:1 complex of two homodimeric subunits, hRRM1 and hRRM2. Prokaryotically expressed and highly purified recombinant human RR subunits, hRRM1 and hRRM2, were used for holoenzyme-based [ 3 H]CDP reduction in vitro assay. Ten new thiosemicarbazones ( 7 – 16 ) were synthesized and screened for their RR inhibitory activity. Two thiosemicarbazones derived from p -hydroxy benzaldehyde ( 9 and 10 ) were found to be active but less potent than the standard, Hydroxyurea (HU). Guided by the activity of compounds 9 and 10 , 11 new thiosemicarbazones ( 17 – 27 ) derived from p -hydroxy benzaldehyde were prepared and screened for their RR inhibitory activity. All the 11 compounds were more potent than HU.