Synthesis of novel curcumin mimics with asymmetrical units and their anti-angiogenic activity

Woo, Ho Bum; Shin, Woon‐Seob; Lee, Seokjoon; Ahn, Chan Mug

doi:10.1016/j.bmcl.2005.05.064

Cited by 44 publications

(15 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As shown in Figure 5, intracellular rhodamine 123 of D407 cells cultured in high glucose was significantly increased when compared with normal glucose controls, indicative of decreased P-gp function. C4, a cell-permeable cinnamoyl compound that reversibly inhibits P-gp efflux function with no noticeable effect on P-gp expression [30], [31], further augmented the high glucose-mediated intracellular accumulation of rhodamine 123. The high glucose-mediated intracellular accumulation of rhodamine 123 was reversed by the pretreatment with PBITU 0.4 mM for 1 h. These effects of PBITU were antagonized with the addition of 1.0 mM L-arginine.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

High Glucose Decreases Expression and Activity of p-glycoprotein in Cultured Human Retinal Pigment Epithelium Possibly through iNOS Induction

Zhang

Sun

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

Inhibition of p-glycoprotein under hyperglycemic conditions has been reported in various barrier tissues including blood-brain barrier, intestine, and kidney, and has been linked to significant clinical complications. However, whether this is also true for the outer blood-retinal barrier constituted by retinal pigment epithelium, or has a role in pathogenesis of diabetic retinopathy is not yet clear. In this study, using cultured human retinal pigment epithelium cell line D407, we found that high glucose exposure induced a significant decrease in p-glycoprotein expression both at mRNA and at protein levels, accompanied by an attenuated p-glycoprotein activity determined by intracellular rhodamine 123 retention. In marked contrast, the expressions of both mRNA and protein levels of inducible nitrate oxide synthase (iNOS) increased, and were accompanied by increased extracellular nitrate/nitrite production by Griess reaction. In addition, mRNA levels of nuclear receptors revealed a decreased expression of pregnane X receptor after the exposure of high glucose. However, the subsequent alterations in production of nitrate/nitrite, functional expression of p-glycoprotein, and mRNA levels of pregnane X receptor were partially blocked when pretreated with S,S′-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea•2HBr (PBITU), a selective iNOS inhibitor. Moreover, the effects of PBITU were antagonized with the addition of L-arginine, a substrate for NO synthesis. Our in vitro results suggest for the first time that iNOS induction plays a novel role in decreased p-glycoprotein expression and transport function at the human outer blood-retinal barrier under hyperglycemic conditions and further support the concept of inhibiting iNOS pathway as a therapeutic strategy for diabetic retinopathy.

show abstract

Section: Resultsmentioning

confidence: 99%

“…Alterations of this barrier have been associated with various sight-affecting conditions, including DR [6], [8], [30]. New therapeutic strategies addressed to modulate RPE impairment are therefore warranted.…”

Section: Discussionmentioning

confidence: 99%

High Glucose Decreases Expression and Activity of p-glycoprotein in Cultured Human Retinal Pigment Epithelium Possibly through iNOS Induction

Zhang

Sun

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Application of synthetic organic chemistry has yielded many derivatives of curcumin. One study of anti-angiogenic properties focused on curcumin mimics whereby the diketone group was replaced by an a, b-unsaturated ketone and the phenolic groups were unsymmetrically replaced by substituted phenyls and other aromatics [168]. Some compounds were identified as more active inhibitors of HUVEC growth and tube formation, but no relation to chemical structure was apparent.…”

Section: Derivatization and Structure-activity Relationshipsmentioning

confidence: 99%

Curcumin: From ancient medicine to current clinical trials

Hatcher

Planalp

Cho

et al. 2008

Cell. Mol. Life Sci.

1,641

1,159

View full text Add to dashboard Cite

Abstract. Curcumin is the active ingredient in the traditional herbal remedy and dietary spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of beneficial properties, including anti-inflammatory, antioxidant, chemopreventive and chemotherapeutic activity. The pleiotropic activities of curcumin derive from its complex chemistry as well as its ability to influence multiple signaling pathways, including survival pathways such as those regulated by NF-kB, Akt, and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and exhibits both pro-and antioxidant activity. It also binds metals, particularly iron and copper, and can function as an iron chelator. Curcumin is remarkably non-toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a therapeutic agent, and is currently in human clinical trials for a variety of conditions, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis and Alzheimers disease.

show abstract

“…[1][2][3] Furthermore, it also exhibits anti-inflammatory, antioxidant, antiviral, and anti-infectious activities and wound healing properties. [4][5][6][7][8] Inhibition of arachidonic acid metabolism by curcumin has been suggested to be a key mechanism for its anticarcinogenic action.…”

mentioning

confidence: 99%

Synthesis of Novel Curcumin Analogues and Their Evaluation as Selective Cyclooxygenase-1 (COX-1) Inhibitors

et al. 2007

View full text Add to dashboard Cite

Curcumin (diferuloyl methane, Chart 1) is a major constituent found in the spice tumeric, which is a dried powder from the rhizomes of Curcuma longa L. Several in vitro and in vivo studies demonstrated suppression, retardation, or inversion of carcinogenesis.1-3) Furthermore, it also exhibits anti-inflammatory, antioxidant, antiviral, and anti-infectious activities and wound healing properties. [4][5][6][7][8] Inhibition of arachidonic acid metabolism by curcumin has been suggested to be a key mechanism for its anticarcinogenic action. The enzyme cyclooxygenase (COX) catalyzes the first two steps in the biosynthesis of prostaglandins (PGs) from the substrate arachidonic acid. At least two forms of this enzyme exist. 9,10) One of these forms, COX-1, is constitutively expressed and is responsible for maintaining normal physiologic function and the PGs produced by this enzyme play a protective role. The other known form of the enzyme, cyclooxygenase-2 (COX-2), is an inducible form and its expression is affected by various stimuli such as mitogens, oncogenes, tumor promoters, and growth factors. 10) COX-2 has been detected in various tumors and its role in carcinogenesis and angiogenesis has been well documented. Therefore, COX-2 is thought to be a promising therapeutic target for cancer. However, current clinical studies of a COX-2-selective inhibitor, rofecoxib (Vioxx), for preventing recurrence of colorectal polyps in patients with a history of colorectal adenomas were discontinued and the drug was withdrawn from the market because its use was associated with an increased incidence of cardiovascular events, such as heart attack and stroke. 11)Very recently, experimental results have also indicated a possible involvement of the other isoform of COX, COX-1, in angiogenesis, thereby providing the rationale for the development of selective COX-1 inhibitors.12,13) These data were also confirmed by in vitro studies in isolated ovine COX-1 and COX-2 enzymes which showed that curcumin and its analogues tetrahydrocurcumin and trimethoxydibenzoylmethane had significantly higher inhibitory effects on the peroxidase activity of COX-1 than that of COX-2.2) Furthermore, a recent report by Gupta et al. 14) has also indicated that COX-1 is overexpressed in a significant number of ovarian cancers. We therefore investigated whether novel curcumin analogues might achieve an even better and more selective COX-1 inhibition than curcumin. Thus, seven analogues of curcumin were synthesized using standard chemical methods. Each analogue (except the intermediate 2) was then tested for COX-1 and COX-2 inhibition in an in vitro model and the resulting inhibition values compared with that of the clinically established selective COX-2 inhibitor celecoxib. Also molecular docking studies were performed to investigate the ligand-protein interactions responsible for the biological data found. Results and DiscussionThe chemical synthesis of the curcumin analogues was carried out following two known pathways. Their basic principle is the same, b...

show abstract

Synthesis of novel curcumin mimics with asymmetrical units and their anti-angiogenic activity

Cited by 44 publications

References 16 publications

High Glucose Decreases Expression and Activity of p-glycoprotein in Cultured Human Retinal Pigment Epithelium Possibly through iNOS Induction

High Glucose Decreases Expression and Activity of p-glycoprotein in Cultured Human Retinal Pigment Epithelium Possibly through iNOS Induction

Curcumin: From ancient medicine to current clinical trials

Synthesis of Novel Curcumin Analogues and Their Evaluation as Selective Cyclooxygenase-1 (COX-1) Inhibitors

Contact Info

Product

Resources

About