title: Synthesis and Bioactivity of a Brasilicardin A Analogue Featuring a Simplified Core.
abstract: An analogue 2 of Brasilicardin A, 1 (BraA), a potent immunosuppressive and cytotoxic agent, was synthesized in which the natural tricyclic skeleton was replaced with a synthetically more accessible substituted tetrahydronaphthalene core. BraA, this analogue (BraL), and cyclosporine A were tested for their ability to inhibit the proliferation of human T cells upon CD3/CD28 activation. Although BraL did not impact T cell activation over the dose range tested, this study shows the inhibitory activity of BraA on human T cells for the first time.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jung
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chamberlain
authors.forename: Pierre
authors.initials: P
authors.lastname: Koch
authors.affiliation: ∥NantWorks LLC, Culver City, California 90232, United States.
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Niazi
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018106:CD28 Antigens; D017252:CD3 Complex; D016572:Cyclosporine / Q000737:chemistry*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D013601:T-Lymphocytes / Q000187:drug effects*
chemical_list: D000617:Aminoglycosides; D000970:Antineoplastic Agents; D018106:CD28 Antigens; D017252:CD3 Complex; D007166:Immunosuppressive Agents; D009281:Naphthalenes; C118259:brasilicardin A; D016572:Cyclosporine