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Michał Zimecki - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative.
Molecules (Basel Switzerland), 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Katarzyna Mieszala, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative
MDPI AG, 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Katarzyna Mieszała, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models
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anti inflammatory properties of an Isoxazole Derivative mzo 2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Iwona Kochanowska, Jolanta Artym, Maja Kocieba, Stanislaw Ryng, Michał ZimeckiAbstract:Abstract Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Anti-inflammatory properties of an Isoxazole Derivative — MZO-2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Maja Kocięba, Iwona Kochanowska, Jolanta Artym, Stanisław Ryng, Michał ZimeckiAbstract:Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic Isoxazole Derivative R-13
Journal of immunotoxicology, 2014Co-Authors: Michał Zimecki, Marcin Mączyński, Maja Kocięba, Jolanta Artym, Bożena Obmińska-mrukowicz, Stanisław RyngAbstract:Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an Isoxazole Derivative R-13 (3,5-dimethyl-Isoxazole[5,4-e]8H-triazepin-4-one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 µg IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA-induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R-13 may be of potential value for reconstitution of the immune function of chemotherapy patients.
Marcin Mączyński - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative.
Molecules (Basel Switzerland), 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Katarzyna Mieszala, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative
MDPI AG, 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Katarzyna Mieszała, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models
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anti inflammatory properties of an Isoxazole Derivative mzo 2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Iwona Kochanowska, Jolanta Artym, Maja Kocieba, Stanislaw Ryng, Michał ZimeckiAbstract:Abstract Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Anti-inflammatory properties of an Isoxazole Derivative — MZO-2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Maja Kocięba, Iwona Kochanowska, Jolanta Artym, Stanisław Ryng, Michał ZimeckiAbstract:Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic Isoxazole Derivative R-13
Journal of immunotoxicology, 2014Co-Authors: Michał Zimecki, Marcin Mączyński, Maja Kocięba, Jolanta Artym, Bożena Obmińska-mrukowicz, Stanisław RyngAbstract:Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an Isoxazole Derivative R-13 (3,5-dimethyl-Isoxazole[5,4-e]8H-triazepin-4-one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 µg IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA-induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R-13 may be of potential value for reconstitution of the immune function of chemotherapy patients.
Iwona Kochanowska - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative.
Molecules (Basel Switzerland), 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Katarzyna Mieszala, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative
MDPI AG, 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Katarzyna Mieszała, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models
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anti inflammatory properties of an Isoxazole Derivative mzo 2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Iwona Kochanowska, Jolanta Artym, Maja Kocieba, Stanislaw Ryng, Michał ZimeckiAbstract:Abstract Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Anti-inflammatory properties of an Isoxazole Derivative — MZO-2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Maja Kocięba, Iwona Kochanowska, Jolanta Artym, Stanisław Ryng, Michał ZimeckiAbstract:Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
Maja Kocięba - One of the best experts on this subject based on the ideXlab platform.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative.
Molecules (Basel Switzerland), 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Katarzyna Mieszala, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models.
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Synthesis, Immunosuppressive Properties, and Mechanism of Action of a New Isoxazole Derivative
MDPI AG, 2018Co-Authors: Marcin Mączyński, Sylwia Borska, Katarzyna Mieszała, Maja Kocięba, Ewa Zaczyńska, Iwona Kochanowska, Michał ZimeckiAbstract:This work describes the synthesis of a new series of Isoxazole Derivatives, their immunosuppressive properties, and the mechanism of action of a representative compound. A new series of N′-substituted Derivatives of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM1–MM10) was synthesized in reaction of 5-amino-N,3-dimethyl-1,2-oxazole-4-carbohydrazide with relevant carbonyl compounds. The Isoxazole Derivatives were tested in several in vitro models using human cells. The compounds inhibited phytohemagglutinin A (PHA)-induced proliferation of peripheral blood mononuclear cells (PBMCs) to various degrees. The toxicity of the compounds with regard to a reference A549 cell line was also differential. 5-amino-N′-(2,4-dihydroxyphenyl)methylidene-N,3-dimethyl-1,2-oxazole-4-carbohydrazide (MM3) compound was selected for further investigation because of its lack of toxicity and because it had the strongest antiproliferative activity. The compound was shown to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF α) production in human whole blood cell cultures. In the model of Jurkat cells, MM3 elicited strong increases in the expression of caspases, Fas, and NF-κB1, indicating that a proapoptotic action may account for its immunosuppressive action in the studied models
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Anti-inflammatory properties of an Isoxazole Derivative — MZO-2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Maja Kocięba, Iwona Kochanowska, Jolanta Artym, Stanisław Ryng, Michał ZimeckiAbstract:Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic Isoxazole Derivative R-13
Journal of immunotoxicology, 2014Co-Authors: Michał Zimecki, Marcin Mączyński, Maja Kocięba, Jolanta Artym, Bożena Obmińska-mrukowicz, Stanisław RyngAbstract:Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an Isoxazole Derivative R-13 (3,5-dimethyl-Isoxazole[5,4-e]8H-triazepin-4-one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 µg IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA-induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R-13 may be of potential value for reconstitution of the immune function of chemotherapy patients.
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anti inflammatory properties of an Isoxazole Derivative mzo 2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Iwona Kochanowska, Jolanta Artym, Maja Kocieba, Stanislaw Ryng, Michał ZimeckiAbstract:Abstract Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Anti-inflammatory properties of an Isoxazole Derivative — MZO-2
Pharmacological Reports, 2016Co-Authors: Marcin Mączyński, Maja Kocięba, Iwona Kochanowska, Jolanta Artym, Stanisław Ryng, Michał ZimeckiAbstract:Background A series of new Isoxazole Derivatives of expected immunosuppressive activities was synthesized. Following in vitro screening in the human cell models, the activity of MZO-2 compound (ethyl N-{4-[(2,4-dimethoxybenzyl)carbamoyl]-3-methylisoxazol-5-yl}acetimidate) in mouse in vivo models was evaluated. Methods In vitro tests included evaluation of: peripheral blood mononuclear cells (PBMC) viability, phytohemagglutinin (PHA)-induced PBMC proliferation and lipopolysaccharide (LPS)-induced tumor necrosis factor α (TNF α) production in whole blood cell cultures. MZO-2 was studied in mice for its effects on: humoral immune response to sheep erythrocytes (SRBC), delayed type hypersensitivity (DTH) to ovalbumin (OVA), contact sensitivity to oxazolone and carrageenan-induced foot pad edema. In addition, the effect of MZO-2 on expression of caspases in Jurkat cells was determined. Results The studied compounds exhibited differential, dose-dependent effects to suppress PHA-induced PBMC proliferation and a weak property to suppress LPS-induced production of TNF α. MZO-2 had no effect on the induction phase of the humoral immune response to SRBC in vitro and in vivo , but moderately suppressed the induction phase of DTH to OVA. Its inhibitory effect on carrageenan-induced paw inflammation was potent. Likewise, MZO-2, applied in ointment, was very effective in reducing ear edema and number of lymphocytes in draining lymph nodes of mice sensitized to oxazolone, comparably to tacrolimus, the reference drug. The expression of caspases 3, 8 and 9 in Jurkat cells was inhibited by the compound. Conclusion MZO-2, applied systemically or locally, may serve as a potential drug for amelioration of inflammatory processes.
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Immune function in cyclophosphamide-treated mice is restored by the T-cell-tropic Isoxazole Derivative R-13
Journal of immunotoxicology, 2014Co-Authors: Michał Zimecki, Marcin Mączyński, Maja Kocięba, Jolanta Artym, Bożena Obmińska-mrukowicz, Stanisław RyngAbstract:Reconstitution of the immune function in chemotherapy patients will lead to decreases in post-operative complications. A preliminary investigation showed that an Isoxazole Derivative R-13 (3,5-dimethyl-Isoxazole[5,4-e]8H-triazepin-4-one) hydrochloride, given in a single oral dose to normal mice, induced significant increases in the content of CD4(+) cells in the spleens and lymph nodes. That observation prompted the authors to assess the immune reconstituting effects of R-13 in mice pre-treated with cyclophosphamide (CP). Mice were given intraperitoneally (IP) a sublethal dose of CP (200 mg/kg) and then R-13 (as 20 µg IP doses, every 3 days post-CP treatment). Control mice, not treated with CP, received R-13 or the vehicle (DMSO in appropriate dilution). Blood leukocyte and splenocyte numbers, blood cell type levels, splenocyte spontaneous and ConA-induced proliferation, and delayed-type hypersensitivity (DTH) to ovalbumin (OVA) were investigated on day 15 post-CP treatment and five R-13 doses. The humoral immune response (antibody-forming cell development to sheep erythrocytes) was measured 30 days post-CP treatment and 10 R-13 doses. In CP-treated mice, five dosings with R-13 led to increases in numbers of splenocytes and blood leukocytes, as well as in spontaneous and ConA-induced splenocyte proliferation, relative to levels in mice that received only CP 15 days earlier. Blood analysis revealed decreases in neutrophil and eosinophil contents and an increased appearance of lymphocyte immature forms in all mice that received the R-13. Both cell-mediated responses to OVA and humoral immune response to sheep erythrocytes in CP-treated hosts were restored. Based on the data here, it is concluded that R-13 may be of potential value for reconstitution of the immune function of chemotherapy patients.
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RM-11, an Isoxazole Derivative, accelerates restoration of the immune function in mice treated with cyclophosphamide.
Pharmacological reports : PR, 2008Co-Authors: Michał Zimecki, Jolanta Artym, Stanisław Ryng, Bożena Obmińska-mrukowiczAbstract:The aim of this study was to evaluate efficacy of an Isoxazole Derivative RM11 to accelerate reconstitution of selected immune activities in cyclophosphamide (CP)-immunocompromised mice. We demonstrated that administration of fifteen 10 mug intraperitoneal doses of RM11, following a sublethal (200 mug/kg) dose of CP, significantly stimulated the number of antibody-forming cells (AFC) to sheep erythrocytes (SRBC) as determined 35 days after the CP treatment. Similarly, treatment of the CP-injected mice with 7 doses of RM11 significantly enhanced generation of delayed type hypersensitivity (DTH) to ovalbumin (OVA). Moreover, in that model, the treatment of mice with RM11 accelerated the process of myelopoiesis. RM11 also counteracted the suppressive action of methotrexate (MTX) in the in vitro model of the humoral immune response to SRBC. The phenotypic studies with fluorocytometer revealed that intraperitoneal 10 mug dose of RM11 significantly elevated the percentage of mature (CD3(+), CD4(+) and CD8(+)) T cells in the spleen and down-regulated the content of CD19(+) cells. We conclude that RM11 may be of potential therapeutic value in restoration of the immune status in patients undergoing chemotherapy.
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by Institute of Pharmacology Polish Academy of Sciences
2008Co-Authors: Michał Zimecki, Jolanta ArtymAbstract:RM-11, an Isoxazole Derivative, accelerates restoration of the immune function in mice treated with cyclophosphamid
