Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells

Federico Medda, Earlphia Sells, Hui Hua Chang, Justin Dietrich, Shashi Chappeta, Breland Smith, Vijay Gokhale, Emmanuelle Meuillet, Christopher Hulme

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

This Letter reports the synthesis and biological evaluation of a collection of aminophthalazines as a novel class of compounds capable of reducing production of PGE2 in HCA-7 human adenocarcinoma cells. A total of 28 analogs were synthesized, assayed for PGE2 reduction, and selected active compounds were evaluated for inhibitory activity against COX-2 in a cell free assay. Compound 2xxiv (R1 = H, R2 = p-CH 3O) exhibited the most potent activity in cells (EC50 = 0.02 μM) and minimal inhibition of COX-2 activity (3% at 5 μM). Furthermore, the anti-tumor activity of analog 2vii was analyzed in xenograft mouse models exhibiting good anti-cancer activity.

Original languageEnglish (US)
Pages (from-to)528-531
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number2
DOIs
StatePublished - Jan 15 2013

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Bioactivity
Dinoprostone
Heterografts
Tumors
Assays
Neoplasms
Adenocarcinoma
aminopyridazine

Keywords

  • Aminophthalazines
  • Cancer
  • COX-2
  • PGE

ASJC Scopus subject areas

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

Cite this

Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells. / Medda, Federico; Sells, Earlphia; Chang, Hui Hua; Dietrich, Justin; Chappeta, Shashi; Smith, Breland; Gokhale, Vijay; Meuillet, Emmanuelle; Hulme, Christopher.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 2, 15.01.2013, p. 528-531.

Research output: Contribution to journalArticle

Medda, Federico ; Sells, Earlphia ; Chang, Hui Hua ; Dietrich, Justin ; Chappeta, Shashi ; Smith, Breland ; Gokhale, Vijay ; Meuillet, Emmanuelle ; Hulme, Christopher. / Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 2. pp. 528-531.
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