Design and synthesis of spirotryprostatin-inspired diketopiperazine systems from prolyl spirooxoindolethiazolidine derivatives.
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.
Bertamino
Alessia
A
Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Via D. Montesano 49, I-80131 Naples, Italy.
Aquino
Claudio
C
Sala
Marina
M
Simone
Nicoletta de
Nd
Mattia
Carlo Andrea
CA
Erra
Loredana
L
Musella
Simona
S
Iannelli
Pio
P
Carotenuto
Alfonso
A
Grieco
Paolo
P
Novellino
Ettore
E
Campiglia
Pietro
P
Gomez-Monterrey
Isabel
I
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
D018797:Cell Cycle Proteins; D054659:Diketopiperazines; D010879:Piperazines; D013141:Spiro Compounds; D053778:Thiazolidines; C478300:spirotryprostatin A