Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

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...

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Bibliographic Details
Published in:	Bioorganic & medicinal chemistry Vol. 18; no. 23; pp. 6248 - 6250
Main Authors:	KRISHNAN, Kesavan, PRATHIBA, Kumari, JAYAPRAKASH, Venkatesan, BASU, Arijit, MISHRA, Nibha, BINGSEN ZHOU, SHUYA HU, YUN YEN
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier 01-12-2008
Subjects:	Analytical, structural and metabolic biochemistry Biological and medical sciences Enzymes and enzyme inhibitors Fundamental and applied biological sciences. Psychology Humans Hydroxyurea - pharmacology Medical sciences Miscellaneous Molecular Structure Oxidation-Reduction Oxidoreductases Pharmacology. Drug treatments Protein Subunits - chemistry Ribonucleotide Reductases - antagonists & inhibitors Ribonucleotide Reductases - chemistry Thiosemicarbazones - chemical synthesis Thiosemicarbazones - chemistry Thiosemicarbazones - pharmacology Human Thiosemicarbazone Enzyme Benzene derivatives p-Hydroxybenzaldehyde thiosemicarbazones In vitro Human recombinant RR subunit Structure activity relation Ribonucleoside-triphosphate reductase RR inhibitory activity Oxidoreductases [3H]CDP reduction assay hRRMI and hRRM2 Ribonucleoside-diphosphate reductase Chemical synthesis
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2008.09.097