title: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Krishnan
authors.forename: Kumari
authors.initials: K
authors.lastname: Prathiba
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
authors.forename: Bingsen
authors.initials: B
authors.lastname: Zhou
authors.forename: Shuya
authors.initials: S
authors.lastname: Hu
authors.forename: Yun
authors.initials: Y
authors.lastname: Yen
mesh_terms: D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D015394:Molecular Structure; D010084:Oxidation-Reduction; D021122:Protein Subunits / Q000737:chemistry; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D021122:Protein Subunits; D013882:Thiosemicarbazones; D012264:Ribonucleotide Reductases; D006918:Hydroxyurea