Synthesis and Characterization of New Curcumin Derivatives as Potential Chemotherapeutic and Antioxidant Agents

Abstract

The purpose of this work was to synthesize a series of symmetrical analogs (CA2-CA7) of curcumin and determine their efficacy as antioxidant and anticancer agents in vitro. The six analogs were successfully synthesized and characterized, one of which, CA6, had not been previously reported in the literature. With the exception of CA2, the analogs had lower predicted aqueous solubilities and higher partition coefficients than curcumin. Two analogs, CA2 and CA3, had lower potencies as anticancer agents compared with curcumin, while CA6 had a slightly higher IC50 value. Two different trends in the antioxidant capabilities of curcumin and its analogs were determined when assessed in vitro or in cell culture. The in vitro DPPH assay clearly showed curcumin as the strongest antioxidant as compared with the analogs when tested at the same concentration or at their IC50 value. The cell culture-based reactive oxygen species/reactive nitrogen species assay indicated that CA3 and CA6 were equal to curcumin in their free radical scavenging ability at the same concentration, but when curcumin and its analogs were tested at their respective IC50 values, CA4 and CA5 showed excellent antioxidant capacities. These results indicate that in cell culture, the ability of these analogs to produce antioxidant effects may be tied to their downstream effects.

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

“…1c ). This is consistent with previous study which showed that the alkylation of ortho-phenolic OH group in curcumin and its derivatives can increase its anti-cancer activity 14 . However, all the OH modified derivatives share the same pharmacophore (α, β-unsaturated ketone group) which imply they have same mode of action 15 16 .…”

“…Previous studies showed that the α, β-unsaturated ketone group of curcumin is critical for its biological activity 3 4 . Structure-activity relationship studies suggested that the derivative of curcumin at the hydroxyl group did not affect the active moiety of the drug 1 14 . To profile and identify the direct targets of curcumin, we introduced an alkyne group at the hydroxyl group position of curcumin to synthesize an activity-based probe, which enables the subsequent linking with a fluorescent dye or biotin ( Fig.…”

A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-inflammatory and Anticancer Activities

“…Its potency was determined due to the morphological changes in SKOV3 cell lines and apoptotic cell death by arresting the cells in S and G2/M phases. In addition, six symmetric curcumin analogues by Ciochina et al (2014) were synthesised by the condensation of the appropriate aldehydes with acetyl acetone-boric oxide complex in ethyl acetate in the presence of tributyl borate and n-butylamine. The analogues were investigated for their antioxidant and anticancer activity, where compounds 11 and 12 demonstrated a greater potential to be chemopreventive agents due to their low cytotoxic potential (Ciochina et al, 2014) 17) and reported its anticancer properties against MCF-7 breast cancer cells which confirmed cell death through cell cycle arrest and induction of apoptosis.…”

Molecular Targets of Naturopathy in Cancer Research: Bridge to Modern Medicine

“…Another approach is the synthesis of novel analogs of nutraceuticals. A number of analogs of various nutraceuticals have been reported [ 40 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. This is another effective strategy to improve the efficacy of nutraceuticals by chemically modifying the structure of the compound, leading to enhanced cytotoxicity, as evidenced by lowered IC 50 values.…”