Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

Kesavan Krishnan; Kumari Prathiba; Venkatesan Jayaprakash; Arijit Basu; Nibha Mishra; Bingsen Zhou; Shuya Hu; Yun Yen

doi:10.1016/j.bmcl.2008.09.097

Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

Kesavan Krishnan, Kumari Prathiba, Venkatesan Jayaprakash, Arijit Basu, Nibha Mishra, Bingsen Zhou, Shuya Hu, Yun Yen

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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 [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.

Original language	English
Pages (from-to)	6248-6250
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.097
Publication status	Published - Dec 1 2008
Externally published	Yes

Keywords

[H]CDP reduction assay
hRRM1 and hRRM2
Human recombinant RR subunit
p-Hydroxybenzaldehyde thiosemicarbazones
RR inhibitory activity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.bmcl.2008.09.097

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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 [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.",

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year = "2008",

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doi = "10.1016/j.bmcl.2008.09.097",

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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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Synthesis and Ribonucleotide reductase inhibitory activity of thiosemicarbazones

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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