Synthetic Approaches to Cytotoxic Amidophosphates, Aminophosphonates, and Aminobisphosphonates with 3,5-Bis(arylidene)piperid-4-one Framework

Abstract

Facile synthetic approaches to a few novel classes of amidophosphates, ω-aminophosphonates, and bisphosphonates having a 3,5-bis(arylidene)piperid-4-one backbone have been elaborated starting from piperid-4-ones functionalized with phosphorus motives followed by aldol-crotonic condensation with a range of (hetero)aromatic aldehydes or via introduction of the corresponding phosphorus function into the preformed NH-3,5-bis(arylidene)piperid-4-ones. Combination of phosphorus-containing moieties possessing inherent bioactivity and cytotoxic 3,5-bis(arylidene)piperid-4-one moiety resulted in the compounds with high antitumor activity towards human carcinoma cell lines Caov3, A549, Scov3, PC3, KB 3-1, and KB 8–5 (IC₅₀ in the range of 1–80 μM).

Keywords:

• Aminobisphosphonates
• aminophosphates
• aminophosphonates
• 3,5-bis(arylidene)piperid-4-ones
• cytotoxic properties
• synthesis

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (DFG No. 436 RUS 113/905/0-1; RO 362/35-1); program of the president of the Russian Federation for young Ph.D. scientists (No. MK-2464.2008.3); program of the Chemistry and Material Science Division of RAS, NIH, via the RIMI program (grant 1P20MD001104-01); and NSF/DMR grant 0934212.