New series of 3, 5-bis(substituted benzylidene)-4-piperidones, 2, 7-bis(substituted benzylidene)cycloheptanones, 1, 5-bis(substituted phenyl)-1, 4-pentadien-3-ones, 1, 7-bis(substituted phenyl)-1, 6-heptadien-3, 5-diones, 1, 1-bis(substituted cinnamoyl)-cyclopentanes, and 1, 1-bis(substituted cinnamoyl)cyclohexanes have been synthesized and tested for their antioxidant activity. Among the tested compounds, compounds II(4), II(9) II(10), II(11), V(1), and V(4) exhibited higher free radical scavenger activity with % inhibition values of 90.71, 91.24, 96.91, 94.26, 99.23, and 99.85%, respectively. Moreover, compound V(1) is the safest member toward peripheral multinuclear neutrophils (PMNs) with a % viability value of 91%. Detailed synthesis, spectroscopic, and biological data are reported.

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In this study, four new curcurmin analogs (compounds 1, 2, 17 and 18) were synthesized. 17 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)N-methylpiperidone] showed high activity with GI50, TGI, and LC50 MG-MID values of 21.3, 70.7, and 97.7 microM, respectively. 18 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)-N-ethylpiperidone] showed the highest activity in this study with GI50, TGI, LC50 MG-MID values of 4.4, 33.8, 89.1 microM, respectively. 18 is even more active than curcumin with GI50, TGI, LC50 MG-MID values of 38.4, 35.6, 66.0 microM; respectively. 8 showed moderate selectivity towards Leukemia cell line-subpanel with a ratio of 5.6 (curcumin ratio: 1.2 for the same subpanel). The in vitro anti-tumor screening reveals that the results go hand in hand with the in vitro free radical scavenging effects. The antioxidant effect of these compounds depends mainly on the stabilization of the formed phenoxy free radical for which the p-hydroxy phenyl moiety is essential. o-substitution by electron-donating groups like the o-methoxy group (and to a even higher degree by the ethoxy group) increases the stability of phenoxy free radical, hence increasing both free scavenging and anti-tumor effects. Increasing the alkyl group chain on the N in the series of substituted N-alkyl piperidones as well as the extension of conjugation, increases the stabilization of phenoxy free radical and thereby the activity towards both free radical scavenging and anti-tumor effects. This may be attributed to an increased positive inductive effect and/or increased lipophilicity of the new compounds, a fact which is proven by the superior activities of compounds 17 and 18.