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A series of novel isoxazole and pyrazoline derivatives has been synthesized and evaluated for their effects on the chemiluminescence and chemotactic activity of human phagocytes. Their effects on the chemotactic migration of isolated polymorphonuclear leukocytes (PMNs) and on the release of reactive oxygen species (ROS) during respiratory burst of human whole blood and PMNs were carried out using the Boyden chamber technique and luminol-based chemiluminescence assay, respectively. Of the compounds tested, compounds 8, 9, 11 and 12 exhibited higher inhibitory activity on the release of ROS (with IC50 values ranging from 5.6 to 8.4 μM) than acetylsalicylic acid (IC50 = 9.5 μ M). These compounds also showed strong inhibitory activity on the migration of PMNs with compound 8 exhibiting an IC50 value lower than that of ibuprofen. The results suggest that some of these isoxazole and pyrazoline derivatives have ability to modulate the innate immune response of phagocytes at different steps, indicating their potential as a source of new immunomodulatory agents.

Objectives: A series of 43 curcumin diarylpentanoid analogues were synthesized and evaluated for their inhibitory effects on the chemiluminescence and chemotactic activity of phagocytes in vitro., Methods: The effects of the compounds on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) were evaluated using a luminol-based chemiluminescence assay and their effect on chemotactic migration of PMNs was investigated using the Boyden chamber technique., Key Findings: Compounds 6, 17, 25 and 30 exhibited significant inhibitory activity on the oxidative burst of PMNs. The presence of methoxy groups at positions 2 and 5, and methoxylation and fluorination at positions 4 and 2 of both phenyl rings, respectively, may contribute significantly to their reactive oxygen species inhibition activity. Compounds 7, 17, 18, 24 and 32 showed strong inhibition of the chemotaxis migration of PMNs. Chlorination at various positions of both phenyl rings of cyclohexanone diarylpentanoid resulted in compounds with potent inhibitory effects on PMN migration., Conclusions: The results suggest that some of these diarylpentanoid analogues are able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)