Synthesis and activity evaluation of the cyclic dipeptides arylidene N-alkoxydiketopiperazines.

ID: ALA4428092

Journal: Bioorg Med Chem

Title: Synthesis and activity evaluation of the cyclic dipeptides arylidene N-alkoxydiketopiperazines.

Authors: Tian X, Feng J, Fan SM, Zhen XL, Han JR, Liu SX.

Abstract: A series of arylidene N-alkoxydiketopiperazines was designed and stereoselectively synthesized via oxime-ether formation and intramolecular acylation. Possible cyclization and acid-catalyzed rearrangement-fragmentation mechanisms were discussed. The crystal structure of the novel diketopiperazine further confirmed the rearrangement mechanism. Most compounds exhibited antitumor activity. Several compounds were more potent against caspase-3. Specifically, compounds 6e, 6g, and 6f inhibited caspase-3 at IC₅₀ values lying within the low micromolar range and demonstrated good selectivity. The binding modes of alkoxydiketopiperazines in the active center of caspase-3 were also discussed based on the molecular docking results.

CiteXplore: 27594550

DOI: 10.1016/j.bmc.2016.08.038

Patent ID: ┄