Dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones as anti-hepatoma agents by inhibiting NF-κB pathway activation

Crystal structure and anti-inflammatory activity of (3E,5E)-1-((4-bromophenyl)sulfonyl)-3-(pyridin-4-ylmethylene)-5-(2-(trifluoromethyl)benzylidene)piperidin-4-one, C25H18BrF3N2O3S

“…For title compound, the expression rate of NO production could reach 55.39 ± 0.91%. The result showed that title compound displayed potential inhibitory effect on LPS-induced NO secretion than PDTC [8,17].…”

“…Curcumin analogues, like the 3,5-bis(arylidene)-4-piperidone (BAPs), contain two α,β-unsaturated keto groups, and have greater predilection or sequential interaction for bio-thiols in tumors rather than normal cells [4,5]. Some BAPs with antitumor and anti-inflammatory properties better than curcumin [6] were reported by our group [7][8][9]. They involve some strong electron-withdrawing groups (-NO 2 , -CN, -CF 3 ) and electrondonating substitutes (-NHAc, -OMe, -CMe 3 ) improving antitumor and anti-inflammatory activity to different extent [10][11][12].…”

“…An asymmetric BAP is obtained by the use of a 4-pyridine substituent, and a trifluoromethylphenyl substituent, respectively (see the figure) [8]. Our interests lie in incorporation of different substituents on the end of N-phenylsulfonyl substituent, and find the desired and improved antitumor and anti-inflammatory activities.…”

Potential multifunctional agents with anti-hepatoma and anti-inflammation properties by inhibiting NF-кB activation

“…In recent years, we have focused on improving modifying the structure of BAPs to optimize the anti-inflammation and antihepatoma capability by inhibiting the NF-jB signalling. We have reported some symmetric or dissymmetric N-substituted-BAPs [12][13][14][15][16][17] and Schiff-base substituted BAPs [18][19][20][21] with improved anti-hepatoma and anti-inflammation activities. For example, the dissymmetric BAP (3E,5E)-3-(2-fluorobenzylidene)-5-(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one(BAP 6d, Figure 1) with different substituent groups on both sides can potentially inhibit HepG2 and THP-1 growth, which were proved by inducing cell apoptosis using flow cytometry and suppressing the growth of HepG2 xenografts 12 .…”

“…For example, the dissymmetric BAP (3E,5E)-3-(2-fluorobenzylidene)-5-(3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one(BAP 6d, Figure 1) with different substituent groups on both sides can potentially inhibit HepG2 and THP-1 growth, which were proved by inducing cell apoptosis using flow cytometry and suppressing the growth of HepG2 xenografts 12 . The further optimized and synthesized dissymmetric N-phenylsulphonyl-BAPs 23 and 76 can prevent the nuclear translocation of NF-jB induced by inflammatory cytokines (lipopolysaccharide (LPS), TNF-a) and exhibit both anti-inflammation and anti-cancer capability in hepatic carcinoma cell lines 13,14 . However, the bioactivity is still not satisfied and the toxicity to the normal cell may be optimized.…”