title: Synthesis and effects of pyrazolines and isoxazoles on the phagocytic chemotaxis and release of reactive oxygen species by zymosan stimulated human neutrophils.
abstract: 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.
authors.affiliation: Drug and Herbal Research Center, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia. ibj@pharmacy.ukm.my.
authors.forename: Syed Nasir Abbas
authors.initials: SN
authors.lastname: Bukhari
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Jantan
authors.forename: Lam Kok
authors.initials: LK
authors.lastname: Wai
authors.forename: Nordin Haji
authors.initials: NH
authors.lastname: Lajis
authors.forename: Faridah
authors.initials: F
authors.lastname: Abbas
authors.forename: Malina
authors.initials: M
authors.lastname: Jasamai
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049449:Luminescence; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D007555:Isoxazoles; D011720:Pyrazoles; D017382:Reactive Oxygen Species; D015054:Zymosan