Inhibition of photophosphorylation by β‐bromo‐β‐nitrostyrene

Brandon, P.C.

doi:10.1016/0014-5793(71)80092-3

Cited by 4 publications

(1 citation statement)

References 13 publications

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“…For example, ␤-bromo-␤-nitrostyrene is a wide-spectrum biocide most frequently used as a fungicide (Mikami et al, 1991). ␤-bromo-␤-nitrostyrene also acts as an inhibitor of energy transfer in photophosphorylation by binding of the nonphosphorylated (Brandon, 1971). A series of sulfonylbenzoyl nitrostyrene derivatives has shown to be specific inhibitors of the epidermal growth factor receptor tyrosine protein kinase (Traxler et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Potent Inhibition of Human Telomerase by Nitrostyrene Derivatives

Kim¹,

Kim²,

Lee³

et al. 2003

Mol Pharmacol

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Telomerase activity is expressed in most types of cancer cells but not in normal somatic cells, suggesting that telomerase may be an important target for cancer chemotherapy. Inhibition of telomerase results in telomere erosion, leading to the subsequent growth arrest of cancer cells followed by senescence or cell death. In this study, we screened a chemical library for the inhibition of human telomerase, identifying three inhibitors. All compounds contained a common nitrostyrene moiety conjugated to different side chains. One of these compounds, 3-(3,5-dichlorophenoxy)-nitrostyrene (DPNS), showed the most potent inhibitory effect, with 50% inhibition at ϳ0.4 M and did not inhibit DNA and RNA polymerases, including retroviral reverse transcriptase. A series of enzyme kinetic experiments suggests that DPNS is a mixed-type noncompetitive inhibitor, with an inhibitor-binding site distinct from the binding sites for the telomeric substrate primer and the deoxynucleoside-5Ј-triphosphates. Extensive propagation of cancer cell line in the presence of DPNS resulted in progressive telomere erosion followed by the induction of senescence phenotype. The results presented here demonstrate that DPNS is a highly selective, small-molecule telomerase inhibitor in vitro and could be useful as a lead molecule for the further development of inhibitors with an improved potential for efficacy in vivo.

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Section: Discussionmentioning

confidence: 99%