title: Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives.
abstract: Based on the spirotryprostatin-A structure, we designed, synthesized, and evaluated different series of compounds belonging to the diketopiperazine structural class as potential cell cycle modulators and cytotoxic agents. Starting from the spirooxoindolthiazolidine scaffold, amide coupling with Pro derivatives and intramolecular cyclization reactions are suitable synthetic methods to generate chemically diverse diketopiperazine system, such as hexahydropyrrolo[1,2-a][1,3]thiazolo[3,2-d]pyrazine-5,10-dione (structure I), hexahydropyrrolo[1,2-a] [1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure II) and spiroindol-2-one[3,3']hexahydro-5,10H-pyrrolo[1,2-a][1,3]thiazolo[3,4-d]pyrazine-5,10-dione (structure III). Some of these compounds, especially those who belong to the series I and II, showed interesting cytotoxic activity.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Via D. Montesano 49, I-80131 Naples, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bertamino
authors.forename: Claudio
authors.initials: C
authors.lastname: Aquino
authors.forename: Marina
authors.initials: M
authors.lastname: Sala
authors.forename: Nicoletta de
authors.initials: Nd
authors.lastname: Simone
authors.forename: Carlo Andrea
authors.initials: CA
authors.lastname: Mattia
authors.forename: Loredana
authors.initials: L
authors.lastname: Erra
authors.forename: Simona
authors.initials: S
authors.lastname: Musella
authors.forename: Pio
authors.initials: P
authors.lastname: Iannelli
authors.forename: Alfonso
authors.initials: A
authors.lastname: Carotenuto
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Pietro
authors.initials: P
authors.lastname: Campiglia
authors.forename: Isabel
authors.initials: I
authors.lastname: Gomez-Monterrey
mesh_terms: D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003500:Cyclization; D054659:Diketopiperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015195:Drug Design; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry*; D013141:Spiro Compounds / Q000737:chemistry*; D053778:Thiazolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D018797:Cell Cycle Proteins; D054659:Diketopiperazines; D010879:Piperazines; D013141:Spiro Compounds; D053778:Thiazolidines; C478300:spirotryprostatin A