Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors

Christophe Guillon; Anna M. Vetrano; Jaya Saxena; Angela Hunter; Geraldine Verderone; Thomas M. Finetti; Jeffrey Wisnoski; Peter W. DeMatteo; Robert D. Rapp; Ned D. Heindel; Laurie B. Joseph; Diane E. Heck; Jeffrey D. Laskin

doi:10.1016/j.bioorg.2020.104128

Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors

Christophe Guillon, Anna M. Vetrano, Jaya Saxena, Angela Hunter, Geraldine Verderone, Thomas M. Finetti, Jeffrey Wisnoski, Peter W. DeMatteo, Robert D. Rapp, Ned D. Heindel, Laurie B. Joseph, Diane E. Heck, Jeffrey D. Laskin

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

5 Scopus citations

Abstract

A set of 4-(R₂-imino)-3-mercapto-5-(R₁)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.

Original language	English (US)
Article number	104128
Journal	Bioorganic Chemistry
Volume	103
DOIs	https://doi.org/10.1016/j.bioorg.2020.104128
State	Published - Oct 2020
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Biology
Drug Discovery
Organic Chemistry

Keywords

Anti-neoplastic agents
HT-29
HeLa
Nitric oxide synthase
Nitrofurantoin
Nitrofurazone
PAM212
PC3
Triazole
iNOS inhibitors

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10.1016/j.bioorg.2020.104128

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Guillon, C., Vetrano, A. M., Saxena, J., Hunter, A., Verderone, G., Finetti, T. M., Wisnoski, J., DeMatteo, P. W., Rapp, R. D., Heindel, N. D., Joseph, L. B., Heck, D. E., & Laskin, J. D. (2020). Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors. Bioorganic Chemistry, 103, Article 104128. https://doi.org/10.1016/j.bioorg.2020.104128

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title = "Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors",

abstract = "A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.",

keywords = "Anti-neoplastic agents, HT-29, HeLa, Nitric oxide synthase, Nitrofurantoin, Nitrofurazone, PAM212, PC3, Triazole, iNOS inhibitors",

author = "Christophe Guillon and Vetrano, {Anna M.} and Jaya Saxena and Angela Hunter and Geraldine Verderone and Finetti, {Thomas M.} and Jeffrey Wisnoski and DeMatteo, {Peter W.} and Rapp, {Robert D.} and Heindel, {Ned D.} and Joseph, {Laurie B.} and Heck, {Diane E.} and Laskin, {Jeffrey D.}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = oct,

doi = "10.1016/j.bioorg.2020.104128",

language = "English (US)",

volume = "103",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

publisher = "Academic Press Inc.",

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T1 - Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors

AU - Guillon, Christophe

AU - Vetrano, Anna M.

AU - Saxena, Jaya

AU - Hunter, Angela

AU - Verderone, Geraldine

AU - Finetti, Thomas M.

AU - Wisnoski, Jeffrey

AU - DeMatteo, Peter W.

AU - Rapp, Robert D.

AU - Heindel, Ned D.

AU - Joseph, Laurie B.

AU - Heck, Diane E.

AU - Laskin, Jeffrey D.

PY - 2020/10

Y1 - 2020/10

N2 - A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.

AB - A set of 4-(R2-imino)-3-mercapto-5-(R1)-4H-1,2,4-triazoles derivatives were synthesized, characterized and evaluated for their ability to inhibit nitric oxide (NO) production in PAM212 mouse keratinocytes, which led to the discovery and the subsequent evaluation of their growth inhibitory cytotoxic potency toward that same mouse cell line together with a number of human cells lines (PC3, HT-29 and HeLa). Some limited SAR could be established for both NO production inhibition potency and growth inhibition cytotoxicity. Noticeably, the compounds designed to be nitrofurantoin mimics were the most potent anti-neoplastic agents.

KW - Anti-neoplastic agents

KW - HT-29

KW - HeLa

KW - Nitric oxide synthase

KW - Nitrofurantoin

KW - Nitrofurazone

KW - PAM212

KW - PC3

KW - Triazole

KW - iNOS inhibitors

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DO - 10.1016/j.bioorg.2020.104128

M3 - Article

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AN - SCOPUS:85088959269

SN - 0045-2068

VL - 103

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

M1 - 104128

ER -

Derivatives of 1,2,4-triazole imines acting as dual iNOS and tumor cell growth inhibitors

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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