Synthesis and activity evaluation of the cyclic dipeptides arylidene N-alkoxydiketopiperazines |
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| Affiliation: | 1. College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People’s Republic of China;2. State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science & Technology, Shijiazhuang 050018, People’s Republic of China;3. College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, People’s Republic of China;1. School of Pharmaceutical Science, Shandong University, 44 West Wenhua Road, Jinan, Shandong Province 250012, PR China;2. Key Lab. of Colloid & Interface Chemistry, Shandong University, Ministry of Education, 250100, PR China |
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| 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. |
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| Keywords: | Synthesis Caspase-3 Antitumor activities Inhibitory activity Molecular docking |
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