2'-Substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis

Abstract

A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1 beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-microM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.

Structure activity relationship studies of anti-inflammatory TMMC derivatives: 4-Dimethylamino group on the B ring responsible for lowering the potency

“…The cytotoxic effect of 2',5'-dihydroxy-4-dimethylaminochalcones (Nam et al, 2003) also was 5-30 fold weaker than other derivatives. 4-Methylaminochalcone also was the least potent at inhibiting biosynthesis of interleukin-1 (Batt et al, 1993), and only inhibited NO production by 15% at 10 µM. One exception is, however, the most potent antimitotic chalcone having 4-dimethylamino group on the B ring (Edwards et al, 1990), putatively because a different mechanism of action functions in blocking mitosis.…”

“…We found several publications dealing with 4-dimethylaminochalcone derivatives (Rojas et al, 2002;Nam et al, 2003;Batt et al, 1993;Edwards et al, 1990). Chalcones with a 4-dimethylamino group on the B ring were much less active than other chalcones.…”

Electrochemical Approach to the Radical Anion Formation from 2′‐Hydroxy Chalcone Derivatives

“…Chemically, chalcone is 1,3-diphenyl-2-propen-1-one and depending on the substitution pattern on the two aromatic rings, a wide variety of pharmacological properties have been identified. These include antioxidant [2,3], anticancer [4,5], antimutagenic [6] and antimalarial [7] activities. On the other hand a number of phenolic antioxidants have been shown to protect against carcinogenesis and mutagenesis [8 -12].…”

A New Cyclopentanol as a Side Product in the Reduction of the Chalcone : Şalkonun Redüksi̇yonunda Bi̇r Yan Ürün Olarak Yeni̇ Bi̇r Si̇klopentanol

“…Documented pharmacological potential of chalcones, such as antibacterial, antiviral, gastric protectant, antimutagenic, retinoid, antimitotic, antioxidant and antiinflamatory activities [1][2][3][4][5], are attributed in part to the alkylating ability of the olefin conjugated with a carbonyl group.…”

“…In this study, a mild reduction was attempted by using zinc in acetic acid instead of catalytic hydrogenation, due to the unavailability of the latter experimental conditions in our laboratories. However, during the course of the reduction of 3-(3,4-dimethoxyphenyl)-l-(3-tolyl)-2-propenone (1) with zinc/acetic acid to obtain the expected 3-(3,4-dimethoxyphenyl)-l-(3-tolyl)propanone (2), another compound proved to be the major product of the reaction at the expense of the desired 2. The structure of this side product, elucidated by high resolution ID and 2D NMR experiments, proved to be a new cyclopentanol derivative (3).…”