Synthesis and Immunosuppressive Activity of Novel Prodigiosin Derivatives
| Autor: | Francesco Colotta, Roberto D'Alessio, Annamaria Isetta, Rossi Arsenia, Alberto Bargiotti, Marcello Tibolla, Pietro Motta, Ermes Vanotti, Orlando Carlini, Mario Rossi, Mario Ferrari, Paola Gnocchi, Nicola Mongelli |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cell Survival
medicine.medical_treatment In Vitro Techniques Prodigiosin Mice Structure-Activity Relationship chemistry.chemical_compound Transduction (genetics) Cell surface receptor Drug Discovery Tumor Cells Cultured medicine Animals Humans Hypersensitivity Delayed Pyrroles Lymphocytes Receptor Chemistry In vitro Mice Inbred C57BL Cytokine Mechanism of action Biochemistry Molecular Medicine Phosphorylation Female medicine.symptom Immunosuppressive Agents Spleen |
| Zdroj: | Journal of Medicinal Chemistry. 43:2557-2565 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm001003p |
| Popis: | Prodigiosins (Ps) represent a family of naturally occurring red pigments characterized by a common pyrrolylpyrromethene skeleton. Some members of this family have been shown to possess interesting immunosuppressive properties exerted with a novel mechanism of action, different from that of currently used drugs. In fact, Ps inhibit phosphorylation and activation of JAK-3, a cytoplasmic tyrosine kinase associated with a cell surface receptor component called common gamma-chain, which is exclusive of all IL-2 cytokine family receptors. Blocking common gamma-chain transduction activity results in a potent and specific immunosuppressive activity. With respect to the interesting and unexploited immunomodulating properties of this family of compounds we initiated a medicinal chemistry program aimed at finding novel prodigiosin derivatives with improved immunosuppressive activity and lower toxicity. Utilizing an unprecedented and flexible way of assembling the prodigiosin frame, a number of new derivatives have been prepared and tested leading to the choice of 4-benzyloxy-5-[(5-undecyl-2H-pyrrol-2-ylidene)methyl]-2, 2'-bi-1H-pyrrole (PNU-156804, 16) as a lead immunosuppressant. |
| Databáze: | OpenAIRE |
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