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Synthesis and Antitumor Activity of Some Curcumin Analogs
Author(s) -
Youssef Khairia M.,
ElSherbeny Magda A.
Publication year - 2005
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200400939
Subject(s) - chemistry , curcumin , moiety , stereochemistry , alkyl , selectivity , antioxidant , scavenging , in vitro , radical , alkoxy group , medicinal chemistry , organic chemistry , biochemistry , catalysis
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 GI 50 , TGI, and LC 50 MG‐MID values of 21.3, 70.7, and 97.7 μM, respectively. 18 [3,5‐bis(4‐hydroxy‐3‐methoxy‐5‐methylcinnamyl)‐ N ‐ethylpiperidone] showed the highest activity in this study with GI 50 , TGI, LC 50 MG‐MID values of 4.4, 33.8, 89.1 μM, respectively. 18 is even more active than curcumin with GI 50 , TGI, LC 50 MG‐MID values of 38.4, 35.6, 66.0 μM; 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 .