Synthesis and evaluation of electron-rich curcumin analogues

Amolins, Michael W.; Peterson, Laura B.; Blagg, Brian S. J.

doi:10.1016/j.bmc.2008.10.057

Cited by 78 publications

(76 citation statements)

References 22 publications

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“…Several studies revealed that curcumin and its congeners manifest antiproliferative activity against various cancers, however, the actual mechanism of the antitumor potential of curcuminoids are still far from being under-stood [13]. With this in mind, it was reported that such compounds of Michael acceptor-type could inhibit cancer cell proliferation in vitro and in vivo via promotion of apoptosis in cancer cells by suppressing cyclin D and endothelial growth factor receptor (EGFR) function, while simultaneously decreasing levels of phosphokinase B (AKT), c-myc, and phospho-AKT (pAKT) [14]. In one of the more significant findings on the anticancer activity of compounds inspired by curcumin, Adams et al [15] announced the superior activity of 2,6-bis(2-fluorobenzylidene)piperidone (EF24) in anti-angiogenesis, cell cycle arrest, and apoptosis of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents

Rostom¹,

Hassan

El‐Subbagh

2009

Archiv der Pharmazie

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A series of 3,5-bis(arylidene)-4-piperidones like chalcone analogues carrying variety of methoxylated aryl groups, pyrazolo[4,3-c]pyridines, pyrido[4,3-d]pyrimidines, and pyrido[3,2-c]pyridines, carrying an arylidene moiety, and some pyrano[3,2-c]pyridines, like flavone and coumarin isosteres, were synthesized and screened for their in-vitro antitumor activity at the National Cancer Institute (NCI, USA). The tested compounds 7, 9, 10, 12, 13, 15, 17, and 19 exhibited a broad spectrum of antitumor activity. Compounds belonging to the pyrazolo[4,3-c]pyridine series proved to be more active than those of the pyrido[3,2-c]pyridine and pyrano[3,2-c]pyridine analogues, in which the monomethoxylated derivatives showed better antitumor activity when compared with their corresponding dimethoxylated congeners. Compound 7 is considered to be the most active member identified in this study with a broad spectrum of activity against 22 different tumor cell lines belonging to the nine subpanels employed, and a particular effectiveness against the breast cancer T-47D cell line (GI 54.7%). The pyrano[3,2-c]pyridine heterocyclic system 19 proved to be the most active antitumor agent among the six-membered fused pyridines, with variable activity against 18 different tumor cell lines, and special activity against the non-small cell lung cancer Hop-92 and ovarian cancer OVCAR-4 cell lines (GI values 63.9 and 48.5%, respectively).

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Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents

Rostom¹,

Hassan

El‐Subbagh

2009

Archiv der Pharmazie

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“…To circumvent this limitation, several approaches were carried out, including the synthesis of curcumin analogues [4,12,13]. Curcumin derivatives were synthesised in order to overcome the pharmacokinetics limitations, with the hope to preserve the same safety profile.…”

Section: Introductionmentioning

confidence: 99%

PAC, a novel curcumin analogue, has anti-breast cancer properties with higher efficiency on ER-negative cells

Al-Hujaily

Mohamed

Al-Sharif

et al. 2010

Breast Cancer Res Treat

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We have investigated here the anti-breast cancer properties of two novel curcumin analogues, EAC and PAC. Apoptosis was assessed by the annexin V/propidium iodide (PI) assay on different breast cancer and normal cells. Immunoblotting analysis determined the effects of these agents on different apoptotic and oncogenic proteins. Furthermore, flow cytometry and Elispot were utilised to investigate the effects on the cell cycle and the production of cytokines, respectively. Breast cancer tumour xenografts were developed in nude mice. Finally, (18)F-radiolabeled PAC and curcumin were produced to study their bioavailability and tissue biodistribution in mice. PAC is five times more efficient than curcumin and EAC in inducing apoptosis, mainly via the internal mitochondrial route. This effect was 10-fold higher against ER-negative as compared to ER-positive cells, and ectopic expression of ERα rendered ER-negative breast cancer cells more resistant to PAC. In addition, PAC delayed the cell cycle at G2/M phase with a stronger effect on ER-negative cells. Moreover, PAC exhibited strong capacity as an immuno-inducer through reducing the secretion of the two major Th2 cytokines IL-4 and IL-10. Importantly, PAC significantly reduced tumour size, and triggered apoptosis in vivo. Furthermore, PAC inhibited survivin, NF-kB and its downstream effectors cyclin D1 and Bcl-2, and strongly up-regulated p21(WAF1) both in vitro and in tumours. Besides, PAC exhibited higher stability in blood and greater biodistribution and bioavailability than curcumin in mice. These results indicate that PAC could constitute a powerful, yet not toxic, new chemotherapeutic agent against ER-negative breast tumours.

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“…[8][9][10][11] During the past few decades, great attention has been paid to structure modification to overcome these problems, and various novel structural analogs of curcumin have been designed for screening. [12][13][14] Dimethoxycurcumin (DMC; Figure 1) is a kind of lipophilic analog of curcumin with all the phenolic hydroxyl groups methylated, and can be easily obtained by synthetic or semi-synthetic methods. 15,16 A variety of experimental studies based on cells and animals have showed that such structural modifications brought about great improvement of DMC in chemical and metabolic stability, as well as anti-inflammatory and anti-tumor activities.…”

Section: Introductionmentioning

confidence: 99%

Preparation, characterization, in vivo pharmacokinetics, and biodistribution of polymeric micellar dimethoxycurcumin for tumor targeting

Liu¹,

Xu²,

Jiang³

et al. 2015

IJN

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Dimethoxycurcumin (DMC) is an analog of curcumin with superior efficacy in various disease models. Currently, drug delivery system research on DMC is very limited, and it has become a huge challenge to realize further developments and clinical applications. In the present study, a kind of amphiphilic block copolymer, N- t -butoxycarbonyl-phenylalanine terminated monomethoxyl poly (ethylene glycol)-b-poly (ε-caprolactone), or mPEG-PCL-Phe(Boc), was prepared from monomethoxyl poly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL) with its hydroxyl terminal chemically converted into N- t -butoxycarbonyl-phenylalanine (Boc-Phe). This copolymer was determined to have a fairly low critical micelle concentration (2.56×10 −3 mg/mL) and passive targeting potential to tumor tissue, and thus was applied to develop a polymeric micellar formulation of DMC for the first time. The DMC-loaded micelles prepared by thin-film hydration method had typical shell–core structure, with an average particle size of 17.9±0.4 nm and a polydispersity index of 0.045±0.011. The drug loading capacity and entrapment efficiency were 9.94%±0.15% and 97.22%±0.18%, respectively, indicating a high-affinity interaction between DMC and the copolymer. At a concentration of 2 mg/mL, the reconstituted micelle solution could be maintained for at least 10 days at room temperature, and displayed a low initial burst release followed by a sustained release in vitro. Pharmacokinetic study in rats revealed that in vivo drug exposure of DMC was significantly increased and prolonged by intravenously administering DMC-loaded micelles when compared with the same dose of free DMC dissolved in dimethyl sulfoxide. Furthermore, in vivo distribution results from tumor-bearing nude mice demonstrated that this micellar formulation significantly changed the biodistribution profile of DMC and increased drug accumulation in tumors. Therefore, the polymeric micellar formulation of DMC, based on the amphiphilic block copolymer, mPEG-PCL-Phe(Boc), could provide a desirable method for delivering DMC, especially for applications in cancer therapy.

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Synthesis and evaluation of electron-rich curcumin analogues

Cited by 78 publications

References 22 publications

Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents

Synthesis and Biological Evaluation of Some Polymethoxylated Fused Pyridine Ring Systems as Antitumor Agents

PAC, a novel curcumin analogue, has anti-breast cancer properties with higher efficiency on ER-negative cells

Preparation, characterization, in vivo pharmacokinetics, and biodistribution of polymeric micellar dimethoxycurcumin for tumor targeting

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