Synthesis and biological activity of aminophthalazines and aminopyridazines as novel inhibitors of PGE2 production in cells |
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| Authors: | Federico Medda Earlphia Sells Hui-Hua Chang Justin Dietrich Shashi Chappeta Breland Smith Vijay Gokhale Emmanuelle J Meuillet Christopher Hulme |
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| Institution: | 1. BIO5 Oro Valley, The University of Arizona, 1580 E. Hanley Blvd., Oro Valley, AZ 85737, United States;2. Departments of Nutritional Sciences and Molecular and Cellular Biology, The University of Arizona, 1515 N. Campbell Ave., Tucson, AZ 85724, United States;3. Department of Pharmacology and Toxicology, College of Pharmacy, The University of Arizona, Tucson, AZ 85721, United States;4. Department of Chemistry & Biochemistry, The University of Arizona, 1306 E. University Blvd., Tucson, AZ 85721, United States |
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| 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-CH3O) 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. |
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