Isoxazole Derivatives as Regulators of Immune Functions
Abstract
1. Introduction
2. Results and Discussion
2.1. Immune Suppression
2.2. Inhibition of Inflammation
2.3. Immunoregulation
2.4. Immunostimulation
3. Conclusions
Funding
Conflicts of Interest
References
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Compound | Structure | Activity | Molecular/Cellular Mechanism of Action | Reference Number |
---|---|---|---|---|
Immunosuppressive actions | ||||
HWA-486/Leflunomide 5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide | Immunosuppressive and anti-inflammatory regulation of autoimmune lymphocytes | COX-2 inhibitor, non-cytotoxic inhibitor of dihydroorotate dehydrogenase | [6] | |
Parecoxib | Anti-inflammatory registered drug | COX-2 inhibitor | [7] | |
8g/5-(4-amino-5-benzoyl-1,2-oxazol-3-yl)-N-[(pyridin-4-yl)methyl]-1,3,4-oxadiazole-2-carboxamide | Inhibits the proliferative response of mouse splenocytes to concanavalin A, suppresses the humoral immune response | N.D. | [8] | |
10f/5-(5-amino-7-phenyl[1,2]oxazolo[4,5-d]pyrimidin-3-yl)-N-[(pyridin-3-yl)methyl]-1,3,4-oxadiazole-2-carboxamide | Stimulates mitogen-induced proliferation of mouse splenocytes, suppresses DTH | N.D. | [8] | |
4d/5-(2-hydroxyethyl)piperazinomethinimino-3-methyl-4-isoxazolecarboxylic acid 4-(4-ethoxyphenyl)-amide | Inhibits the DTH and humoral immune response to SRBC in vitro and in vivo | N.D. | [9] | |
RM-33/3,5,7-trimethyl-5,6,7,8-tetrahydro-4H-[1,2]oxazolo[5,4-e][1,2,4]triazepin-4-one | Inhibits LPS-induced TNF-α and IL-6 activity inhibits antibody production | * Stimulation of caspase 9 expression in thymocytes and splenocytes and Fas in bone marrow cells and splenocytes, inhibition of ERK1 and p38g in bone marrow cells | [10] | |
1020/5-{[(4-hydroxyphenyl)methylidene]amino}-3-methyl[1,2]oxazolo[5,4-d]pyrimidin-4(5H)-one | Displays strong immunosuppressive action, inhibits polyclonal antibody production | N.D. | [11] | |
1025/5-(cyclohexylideneamino)-3-methyl[1,2]oxazolo[5,4-d]pyrimidin-4(5H)-one | Shows immunosuppressive property, lowers polyclonal antibody production | N.D. | [11] | |
M5/2-[(5-amino-3-methylisoxazol-4-yl)carbonyl]-N-(4-chlorophenyl)hydrazinecarboxamide | Inhibits antibody production in mice | N.D. | [12] | |
RM56/5-(5-amino-3-methyl-1,2-oxazol-4-yl)-1,3,4-oxadiazol-2-amine | Inhibits the humoral immune response, the carrageenan reaction and proliferation of lymphocytes | N.D. | [13] | |
MO5/5-amino-3-methyl-N-[(4-methylphenyl)methyl]-1,2-oxazole-4-carboxamide | Inhibits the humoral immune response in vitro | Inhibitor of TNFα production | [14] | |
5-amino-3-methyl-1,2-oxazole-4-carbohydrazide | Modulates the content of T cell subsets and B cells in lymphoid organs, and elevates the humoral immune response in mice | Upregulation of fractalkine (CX3CL1) and IL-17F, and downregulation of IL-10 and TLR4 | [15] | |
MM3/5-amino-N′-[2-(2,4-dihydroxyphenyl)ethylidene]-N,3-dimethyl-1,2-oxazole-4-carbohydrazide | Inhibits the mitogen-induced proliferation of PBMC and LPS-induced TNF α production in human blood cell culture | Strong increases in the expression of caspases, Fas, and NF-kB1 | [16] | |
Immune regulators | ||||
HWA-486/Leflunomide 5-methyl-N-[4-(trifluoromethyl)phenyl]-1,2-oxazole-4-carboxamide | Suppresses T cell-dependent B-cell responses, does not affect T-independent B-cell function | COX-2 inhibitor | [17] | |
5-amino-3-methyl-1,2-oxazole-4-carbohydrazide | Modulates T cell subset composition and the levels of B cells in lymphoid organs, and enhances anti-SRBC humoral immune responses in mice | Modulation of T and B cell content in lymphatic organs | [18] | |
06K/2-(5-amino-3-methyl-1,2-oxazole-4-carbonyl)-N-(4-chlorophenyl)hydrazine-1-carbothioamide | Induces lymphopoiesis and the generation of regulatory T-cells, stimulates the humoral immune response, decreases the DTH reaction | Increases percentage of CD8+ and regulatory CD4+CD25+Fox3+ T cells in spleens and lymph nodes | [19] | |
01K/2-(5-amino-3-methyl-1,2-oxazole-4-carbonyl)-N-phenylhydrazine-1-carbothioamide | Regulates proliferation of thymocytes, splenocytes, and lymph node cells | Regulation of IL-1β and TNF-α production in peritoneal cell cultures | [20] | |
MO5/5-amino-3-methyl-N-[(4-methylphenyl)methyl]-1,2-oxazole-4-carboxamide | Inhibits the humoral immune response in vitro | Inhibition of TNFα production | [14] | |
Anti-inflammatory | ||||
5-amino-N-(4-ethoxyphenyl)-3-methyl-1,2-oxazole-4-carboxamide | Lowers carrageenan-induced paw edema, exhibits antibacterial activity | N.D. | [21] | |
5-benzamido-N-(4-chlorophenyl)-3-methyl-1,2-oxazole-4-carboxamide | Shows anti-inflammatory activity in the carrageenan-induced reaction, has antibacterial properties | N.D. | [21] | |
VGX-1027 (S,R)-(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)acetic acid | Suppresses carrageenan-induced pleurisy, LPS-induced lethality, and type II-collagen-induced arthritis | Suppression of TNF α, IL-1β, MIF, inhibition of NFκB and p38, and upregulation of ERK signaling | [22] | |
N-(2-(Benzo[d][1,3]dioxol-5-yl)ethyl)-5-(biphen-4-yl)-isoxazole-3-carboxamide | Protects against experimental colitis | Inhibition of FAAH (fatty acid amide hydrolase)) | [23] | |
2b/5-(3-methylthiophen-2-yl)-3-(3,4,5-trimethoxyphenyl)-1,2-oxazole | Inhibits tumor growth, peritoneal angiogenesis, and ascite formation in Erlich carcinoma mouse model | Inhibitory activity toward lipooxygenase (LOX) and COX-2 | [24] | |
39/4-(4-Chlorophenyl)-5-[4-(quinolin-2-ylmethoxy)phenyl]isoxazol-3-carboxylic acid 40/4-(4-Chlorophenyl)-5-[4-(benzothiazol-2-ylmethoxy)phenyl] isoxazol-3-carboxylic acid | Anti-inflammatory agent | Inhibitory activity against cellular 5-LO (5-lipoxygenase) product synthesis | [25] | |
ISO-1/(S,R)-methyl [3-(4-oxocyclohexa-2,5-dien-1-ylidene)-1,2-oxazolidin-5-yl]acetate | Blocks corticosteroid-insensitive lung inflammation and airway hyper-responsiveness) suppresses lung inflammation in ozone-exposed mice, in contrast to dexamethasone | Inhibition of migration inhibitory factor (MIF) function | [26] | |
Cpd #15/(16S,17R)-30-bromo-6,9-difluoro-11b,21-dihydroxy-40H-pregna-1,4-dieno[16,17-d]isoxazole-3,20-dione | Inhibits eosinophilic infiltration in a model of allergen-induced pulmonary inflammation in rats | Inhibits LPS-induced nitric oxide production | [27] | |
7a/N-(4-(isoxazol-5-yl)phenyl)-4,6-di(piperidin-1-yl)-1,3,5-triazin-2-amine | Reduces carrageenan-induced mice paw edema in comparison to celecoxib | COX-2 inhibitor | [28] | |
MZO-2/ethyl N-(4-{[(2,4-dimethoxyphenyl)methyl]carbamoyl}-3-methyl-1,2-oxazol-5-yl)ethanimidate | Inhibits carrageenan-induced footpad inflammation and the contact sensitivity in mice to oxazolone when applied in ointment | Suppression of LPS-induced TNFα, and the expression of caspases 3, 8, and 9 in Jurkat cells | [29] | |
4-(2-(4-(1H-benzimidazol-2-yl)phenyl)hydrazono)-1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one | Demonstrates analgesic activity and protection in paw edema test, is comparable with that of the reference drug Diclofenac | N.D. | [30] | |
Isoxazole-mercaptobenzimidazole hybrids | Is analgesic and anti-inflammatory activity in vivo | N.D. | [31] | |
(3S,3aR,6aS)-5-benzyl-3-(1H-indol-3-yl)-2-phenyl-hexahydro-2H-pyrrolo[3,4-d][1,2]oxazole-4,6-dione (9ª) | Increases survival in a mouse model of sepsis | Inhibition of LPS-induced TNF α and IL-6 production in macrophage THP-1 cells | [32] | |
Immunostimulatory | ||||
HAB-439/(3-phenyl-4,5-dihydro-1,2-oxazol-5-yl)phosphonic acid | Stimulates DTH response to Salmonella typhimurium and Listeria monocytogenes | Inhibitor of aminopeptidase B | [33] | |
RM-11/3,5-dimethyl-5,6-dihydro-4H-[1,2]oxazolo[5,4-e][1,2,4]triazepin-4-one | Stimulates mitogen-induced splenocyte proliferation and accelerates the restoration of the humoral and cellular immune response in cyclophosphamide-treated mice | N.D. | [34,35] | |
R-11/3,5-dimethyl-5,8-dihydro-4H-[1,2]oxazolo[5,4-e][1,2,4]triazepin-4-one | Recruits CD19+ B and accelerates the development of both types of the immune response in immunocompromised mice | Stimulation of LPS-induced IL-6 production in human whole blood cultures | [36] | |
R-13/3,5-dimethyl-5,8-dihydro-4H-[1,2]oxazolo[5,4-e][1,2,4]triazepin-4-one hydrochloride | Recruits CD4+ T cells and accelerates the restoration of both types of the immune response in immunocompromised mice | N.D. | [37] | |
M4/.2-(5-amino-3-methyl-1,2-oxazole-4-carbonyl)-N-(prop-2-en-1-yl)hydrazine-1-carbothioamide | Enhances the mitogen-induced proliferative response of human PBMC | N.D. | [12] | |
5-amino-3-methyl-1,2-oxazole-4-carbohydrazide | Stimulates mitogen-induced proliferation of splenocytes and lymph node cells | Increase of LPS-induced induced IL-1β production by peritoneal cells | [38] | |
8e/3-(4-methoxyphenyl)-4(3-hydroxy-4-carboxybenzoyl)-5-(3-chlorophenyl)-4,5-dihydrodihydroisoxazoline | Augments the proliferative response of human and mouse lymphocytes | Increased IL-2 secretion | [39] |
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Zimecki, M.; Bąchor, U.; Mączyński, M. Isoxazole Derivatives as Regulators of Immune Functions. Molecules 2018, 23, 2724. https://doi.org/10.3390/molecules23102724
Zimecki M, Bąchor U, Mączyński M. Isoxazole Derivatives as Regulators of Immune Functions. Molecules. 2018; 23(10):2724. https://doi.org/10.3390/molecules23102724
Chicago/Turabian StyleZimecki, Michał, Urszula Bąchor, and Marcin Mączyński. 2018. "Isoxazole Derivatives as Regulators of Immune Functions" Molecules 23, no. 10: 2724. https://doi.org/10.3390/molecules23102724
APA StyleZimecki, M., Bąchor, U., & Mączyński, M. (2018). Isoxazole Derivatives as Regulators of Immune Functions. Molecules, 23(10), 2724. https://doi.org/10.3390/molecules23102724