TY - JOUR
T1 - Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones
AU - Krishnan, Kesavan
AU - Prathiba, Kumari
AU - Jayaprakash, Venkatesan
AU - Basu, Arijit
AU - Mishra, Nibha
AU - Zhou, Bingsen
AU - Hu, Shuya
AU - Yen, Yun
PY - 2008/12/1
Y1 - 2008/12/1
N2 - 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 [3H]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.
AB - 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 [3H]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.
KW - [H]CDP reduction assay
KW - hRRM1 and hRRM2
KW - Human recombinant RR subunit
KW - p-Hydroxybenzaldehyde thiosemicarbazones
KW - RR inhibitory activity
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U2 - 10.1016/j.bmcl.2008.09.097
DO - 10.1016/j.bmcl.2008.09.097
M3 - Article
C2 - 18976907
AN - SCOPUS:55549087863
SN - 0960-894X
VL - 18
SP - 6248
EP - 6250
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 23
ER -
