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).

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