Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin

Yadav, Babasaheb D.; Taurin, Sébastien; Rosengren, Rhonda J.; Schumacher, Marc; Diederich, Marc; Somers-Edgar, Tiffany J.; Larsen, Lesley

doi:10.1016/j.bmc.2010.07.063

Cited by 93 publications

(93 citation statements)

References 31 publications

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“…Of these two compounds showed potent cytotoxicity: 3,5-bis (pyridine-4-yl)-1-methylpiperidin-4-one (RL66) and; 3,5-bis (3,4,5-trimethoxybenzylidene)-1-methylpiperidin-4-one (RL71) ( Table 3). Both had IC 50 values below 1 mM in oestrogen receptor negative cell lines (MBA-MB-231 and MDA-MB-468) [18]. RL66 at 2 µM caused cell cycle arrest, a decrease in HER-2/neu phosphorylation, increased p27 levels, caspase 3 cleavage and apoptosis in SKBr3 cells after 48 h [62].…”

Section: Synthetic Derivativesmentioning

confidence: 94%

“…Curcumin, obtained from the roots and rhizomes of the perennial plant Curcuma longa, is cytotoxic towards both ER+ and TNBC cells [18][19][20]. For example, curcumin inhibited the proliferation of ER-MDA-MB-468 and MDA-MB-231 cells, with IC 50 values of 1 and 7.6 µM, respectively [19,21].…”

Section: Curcumin As a Chemotherapeuticmentioning

confidence: 99%

“…This imparts a rigid confirmation that has led to a broad spectrum of antitumor activity. The second generation curcumin derivative 2,6-bis ((3-methoxy-4-hydroxyphenyl) methylene)-cyclohexanone (BMHPC) was cytotoxic toward ER-breast cancer cells (IC 50 of 5.0 μM) and displayed anti-angiogenic properties in human and murine endothelial cell lines [18,21,49,50,[52][53][54][55][56][57][58][59].…”

Section: Synthetic Derivativesmentioning

confidence: 99%

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Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers

Cridge¹,

Larsen²,

Rosengren³

2013

Oncol Discov

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Curcumin, a spice found in curry powder, is receiving considerable attention as a possible chemopreventative and chemotherapeutic. This review considers the evidence for the use of curcumin as a treatment for breast cancer, particularly triple negative breast cancers (lacking ER, PR and HER2) which are resistant to many current treatments. Evidence suggests that curcumin suppresses the growth of breast cancers both in vitro and in vivo. In ER-cell lines curcumin causes apoptosis via a range of mechanisms at concentrations ranging between 1 µM and 7.6 µM depending on the cell line and system. In xenograft models, curcumin has been shown to be effective but is limited by its bioavailability. This can be improved by nanotechnologies such as micelles. Studies with micelles have shown that these systems increase the uptake and cytotoxicity of curcumin in vitro. In xenotransplantation models micelles improved bioavailability and increased the half-life of curcumin while showing increases in apoptosis in implanted tumours. The last area discussed is the development of curcumin derivatives. Many of these show increased cytotoxicity (less than 1 µM) and improved pharmacokinetic profiles in vivo. The most potent of these compounds developed to date are RL66 and RL71 with IC 50 values less than 1 µM across a range of breast cancer cell lines, decreased metastasis in a xenograft model, decreased angiogenesis markers and improved tumour growth inhibition as compared to curcumin. Overall, this review concludes that curcumin and its derivatives show future potential as a powerful broad-spectrum treatment for breast cancer.

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Section: Synthetic Derivativesmentioning

confidence: 94%

Section: Curcumin As a Chemotherapeuticmentioning

confidence: 99%

Section: Synthetic Derivativesmentioning

confidence: 99%

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Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers

Cridge¹,

Larsen²,

Rosengren³

2013

Oncol Discov

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Section: Introductionmentioning

confidence: 99%

“…Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells.…”

mentioning

confidence: 99%

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Wei

Cui

et al. 2012

Oncology Letters

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Abstract. Curcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Six cyclohexanone analogues of curcumin (A 1 -A 6 ) were investigated for their effects on growth and apoptosis in PC-3 human prostate cancer cells. The ability of these compounds to inhibit NF-κB activity in PC-3 cells was also determined. Five out of the six curcumin analogues (A 2 -A 6 ) had stronger inhibitory effects compared to curcumin on the growth of cultured PC-3 cells. Compounds A 2 -A 6 also had stronger stimulatory effects on apoptosis in PC-3 cells than curcumin, and these curcumin analogues more potently inhibited NF-κB activity than curcumin. The inhibitory effects of these compounds on NF-κB activity correlated with their effects on growth inhibition and apoptosis stimulation in PC-3 cells. The results of the present study provide a rationale for in vivo studies with A 2 -A 6 using suitable animal models of prostate cancer. IntroductionCurcumin is a non-nutritive yellow pigment found in the spice turmeric, which is derived from the rhizome of the plant Curcuma longa Linn. Curcumin lacks toxicity in humans (1), and extensive research over several decades has revealed that curcumin possesses anticancer, anti-inflammatory, antioxidant, antiviral and anti-bacterial activities (2,3). Curcumin suppressed cell proliferation or induced apoptosis in cultured prostate cancer cells and other types of cancer cells (4-10). Curcumin also inhibited prostate carcinogenesis (11). Studies from our laboratory and those of other authors have demonstrated enhanced anticancer activities of curcumin when combined with other anticancer agents (12-14). Findings of earlier studies showed that curcumin exerts a wide range of anticancer effects by modulating a diversity of signaling pathways, including nuclear factor-κB (NF-κB) and other pathways (15)(16)(17)(18)(19)(20). Curcumin has entered clinical trials for certain types of human cancer (21-23). However, the clinical efficacy of curcumin is limited, which is likely to be due to its low bioavailability (21-23). It was suggested that the β-diketone moiety of curcumin causes instability and poor metabolic properties (24-26). Enhanced stability was found in curcumin analogues by deleting the β-diketone moiety of the molecule (27). Recently, it was demonstrated that the cyclohexanone analogues of curcumin have enhanced stability in biological medium compared to curcumin (28). The cyclohexanone-containing curcumin analogue 2,6-bisp[(3-methoxy-4-hydroxyphenyl)methylene)]-cyclohexanone was found to be more potent than curcumin for inhibiting NF-κB in human breast cancer cells in vitro (29).In an earlier study, we synthesized a series of cyclohexanone curcumin analogues and determined their inhibitory effect on the activity of aldose reductase (30). In the present study, we investigated the effects of these curcumin analogues on the growth and apoptosis of human prostate cancer PC-3 cells. We also determined the inhibitory effect ...

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Recent Advances of Curcumin Derivatives in Breast Cancer

Yin

Tan

Wei

et al. 2022

Chemistry & Biodiversity

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Curcumin is a potential plant-derived drug for the treatment of breast cancer. Poor solubility and bioavailability are the main factors that limit its clinical application. Various structural modification strategies have been developed to improve the anti-breast cancer activity of curcumin. This review focuses on the difference of modification sites and heterocyclic/non-heterocyclic modifications to systematically summarize curcumin derivatives with better anti-breast cancer activity.

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Synthesis and cytotoxic potential of heterocyclic cyclohexanone analogues of curcumin

Cited by 93 publications

References 31 publications

Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers

Curcumin and its derivatives in breast cancer: Current developments and potential for the treatment of drug-resistant cancers

Effects of cyclohexanone analogues of curcumin on growth, apoptosis and NF-κB activity in PC-3 human prostate cancer cells

Recent Advances of Curcumin Derivatives in Breast Cancer

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