Curcuminoids versus Pyrazole‐Modified Analogues: Synthesis and Cytotoxicity against HepG2 Cancer Cell Line

Abstract

Twenty compounds including curcuminoids and their pyrazolemodified analogues were synthesized in a two-step reaction: (i) condensation between benzaldehyde derivatives and pentane-2,4-dione and (ii) pyrazole cyclization of the 1,3-diketone group in the resulting curcuminoids with hydrazine hydrate. The synthesized compounds were assayed for in vitro anticancer activity against HepG2 cancer cell line by determining their half-maximal inhibitory concentration (IC 50). Pyrazole curcuminoid (1 a, IC 50 = 1.53 � 0.11 μM) was found to be the most potent molecule against the cancer cells. The pyrazole curcuminoids (1 a-3 a, 5 a) significantly exhibited between 2-to 23-fold higher anticancer activities when compared with their parent structures (1-3, 5). However, the class of fluorinated analogues (7-10; 7 a-10 a) displayed inactivities or activities close to those of respecting compounds (1-6; 1 a-6 a). Structure-activity relationship analysis indicated that the phenolic motif is responsible for inhibition of cell growth whereas the fluoro/methoxy substituents on the aromatic rings have insignificant contributions to inhibitory activities against HepG2.

Synthesis and cytotoxicity of substituted aromatic curcuminoids against human oral epidermal carcinoma-KB cell line

“…The published procedurewas used to carry out the synthetic procedure of curcuminoids (1-6) bearing various substituents on aromatic rings 12,13,18,19 (Figure 1). A mixture of boron oxide (10.0 mmol) and pentane-2,4-dione (10.0 mmol) in ethyl acetate (20.0 mL) was stirred at 70 • C for 1 h in a 100-mL two-neck round-bottom flask to yield the solution of acetylacetone-borate complex.…”

“…Curcumin (1), a constituent of turmeric powder derived from the rhizome of C. longa, is an attractive compound with broad-spectrum capacities including anti-oxidant 5 , anti-inflammatory 6 , and antitumour 7 activities. In particular, many studies reported that curcumin exhibited anti-cancer activity in a wide range of human cancers [8][9][10][11][12][13][14][15] . In addition, curcumin is pharmacologically safe as large quantities of curcumin, up to 10 g per day, can be consumed without inflicting toxicity 16 .…”

“…J.; 24(2):1918-1923. ability 17 . To overcome these limitations, chemical modification of the curcumin structure is one of the promising approaches to explore curcumin-based analogs, which improve the therapeutic profile of the mother compound [8][9][10][11][12] . Structure-activity relationship (SAR) analysis on curcumin analogs revealed that the aromatic ring and its substituents are necessary for biological activities [10][11][12][13] .…”

“…To overcome these limitations, chemical modification of the curcumin structure is one of the promising approaches to explore curcumin-based analogs, which improve the therapeutic profile of the mother compound [8][9][10][11][12] . Structure-activity relationship (SAR) analysis on curcumin analogs revealed that the aromatic ring and its substituents are necessary for biological activities [10][11][12][13] . In view of this, benzaldehyde analogs bearing various functional groups in the phenyl ring were selected as starting materials to condense with pentane-2,4-dione under basic conditions to afford analogs of curcumin [10][11][12][13]18,19 .…”

“…Structure-activity relationship (SAR) analysis on curcumin analogs revealed that the aromatic ring and its substituents are necessary for biological activities [10][11][12][13] . In view of this, benzaldehyde analogs bearing various functional groups in the phenyl ring were selected as starting materials to condense with pentane-2,4-dione under basic conditions to afford analogs of curcumin [10][11][12][13]18,19 . Within this framework, curcumin analogs containing hydroxy/methoxy/fluorine groups on phenyl rings were synthesized in our work, and their in vitro anticancer activities against oral cancer cells (KB) were assessed.…”