4-(β-Arylvinyl)-3-(β-arylvinylketo)-1-ethyl-4-piperidinols and Related Compounds:  A Novel Class of Cytotoxic and Anticancer Agents

Abstract

The syntheses of a series of 1-aryl-5-diethylamino-1-penten-3-one hydrochlorides 1 and 1-aryl-3-diethylamino-1-propanone hydrochlorides 4 were accomplished. Attempts to prepare the corresponding bis(5-aryl-3-oxo-4-pentenyl)ethylamine hydrochlorides 2 and bis(3-aryl-3-oxopropyl)ethylamine hydrochlorides 5 led to the formation of a series of 4-(beta-arylvinyl)-3-(beta-arylvinylketo)-1-ethyl-4-piperidi nol hydrochlorides 9 and 4-aryl-3-arylketo-1-ethyl-4-piperidinol hydrochlorides 11, most of which were converted subsequently into the corresponding quaternary ammonium salts 10 and 12, respectively. The structures of these compounds were determined by 1H NMR spectroscopy and confirmed by X-ray crystallography of representative molecules. Most compounds displayed significant cytotoxicity toward murine P388 and L1210 cells as well as human tumors. In general, Mannich bases containing olefinic bonds were more cytotoxic than the analogues without this functional group, while the piperidines 9 and 11 were more potent than the acyclic analogues 1 and 4, respectively. Correlations were noted between various physicochemical constants in the aryl rings and cytotoxicity. Compound 9d displayed promising in vivo activity against colon cancers. This study has revealed that the piperidines 9 and 11 constitute new classses of cytotoxic agents.

Anti-angiogenic activity of the flavonoid precursor 4-hydroxychalcone

“…The structure and stereochemistry of the compounds were characterized by elemental analysis, IR and NMR methods. The synthesized Q797 and 4-hydroxyindanone had melting points in accord with the literature values (Dimmock et al, 1998).…”

Role of Donor−Acceptor Strengths and Separation on the Two-Photon Absorption Response of Cytotoxic Dyes: A TD-DFT Study

“…The family of piperidone and cyclohexanone derivatives (Figure 1b) we considered show significant TPA activities, even though these are not the best cross sections among known organic chromophores. However, compounds 1-17 combine good nonlinear response with important cytotoxic properties [52][53][54][55][56]64 and may, therefore, serve as a synthetic base for future photodynamic therepy drugs.…”

The Design and Cytotoxic Evaluation of Some 1‐Aryl‐3‐isopropylamino‐1‐propanone Hydrochlorides towards Human Huh‐7 Hepatoma Cells

“…The use of a primary amine means that the initial Mannich base formed could react further with a ketone and formaldehyde [22]. For example, in the case of the attempted synthesis of series 1, the formation of the corresponding N,N-bis(3-aryl-3-oxopropyl)isopropylamine hydrochlorides may have occurred.…”