Phospholipase A2 inhibitor

The family Caprifoliaceae comprises approx 400 species, of which Lonicera japonica Thunb., Lonicera affinis Hook and Arn, Lonicera confusa DC, Sambucus javanica Reinw. ex. Bl, Sambucus sieboldiana (Miq.) Graebn, and Weigela floribunda (Sieb. and Zucc.) K. Koch, are used to treat inflammatory conditions in Asia and the Pacific. There is an expanding body of evidence to suggest that biflavonoids from this family might hold some potential as phospholipase A2 inhibitors. One such compound is ochnaflavone from Lonicera japonica Thunb. 

Wallner, B.P., Mattaliano, R.J., Hession, C., Cate, R.L., Tizard, R., Sinclair, L.K., Foeller, C., Chow, E.P., Browning, J.L., Ramachandran, K.L. and Pepinsky, R.B. (1986). Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential anti-inflammatory activity. Nature 320 77-80. 

Ortiz, A.R., Pastor, M., Palomer, A., Cruciani, G., Gago, F., and Wade, R.C. Reliability of comparative molecular field analysis models effects of data scaling and variable selection using a set of human synovial fluid phospholipase A2 inhibitors. /. Med. Chem. 1997, 40, 1136-1148. 

LTC4 and LTD4 are potent bronchoconstrictors and are recognized as the primary components of the slow-reacting substance of anaphylaxis (SRS-A) that is secreted in asthma and anaphylaxis. There are four current approaches to antileukotriene drug development 5-LOX enzyme inhibitors, leukotriene-receptor antagonists, inhibitors of FLAP, and phospholipase A2 inhibitors. 

The cytostolic phospholipase A2 inhibitor tauropinnaic acid (229) was isolated from the Okinawan bivalve Pima muricata (pen shell). The structure and stereochemistry at all but one centre were elucidated by interpretation of spectroscopic data [234]. 

Farooqui A. A., Ong W. Y., and Horrocks L. A. (2004). Neuroprotection abilities of cytosolic phospholipase A2 inhibitors in kainic acid-induced neurodegeneration. Curr. Drug Targets Cardiovasc. Haematol. Disord. 4 85-96. 

St-Gelais F., Menard C., Congar P., Tmdeau L. E., and Massicotte G. (2004). Postsynaptic injection of calcium-independent phospholipase A2 inhibitors selectively increases AMPA receptor-mediated synaptic transmission. Hippocampus 14 319-325. 

M Nakamura, T Kino, K Niko, S Kiyoto, M Okuhara Phospholipase A2 inhibitor. Japanese Patent 2,255,615, 1990. 

XII. Secretory Phospholipase A2 Inhibitors A. (V-Benzyl Tetracyclic-based Medicaments Title sPLA2 Inhibitors... 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

M. T. Pisabarro, A.R. Ortiz, A. Palomer, F. Cabre, L. Garcia, R.C. Wade, F. Gago, D. Mauleon, G. Carganico, Rational Modification of Human Synovial Fluid Phospholipase A2 Inhibitors,/. Med. Chem. 1994, 37, 337-341. 

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