New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy.

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Pommery N, Taverne T, Telliez A, Goossens L, Charlier C, Pommery J, Goossens JF, Houssin R, Durant F, Henichart JP

New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy.

J Med Chem. 2004 Dec 2;47(25):6195-206.

PubMed ID

15566290 [ View in PubMed

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Abstract

The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	36	N/A	N/A	Details