Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative

Li, Ling; Rossoni, Giuseppe; Sparatore, Anna; Lee, Lin Chiou; Soldato, Piero Del; Moore, Philip K.

doi:10.1016/j.freeradbiomed.2006.12.011

Cited by 312 publications

(317 citation statements)

References 33 publications

Supporting

Mentioning

298

Contrasting

Unclassified

Order By: Relevance

“…The compounds S-diclofenac and S-sulindac were prepared adding to the respective free acids, ADT-OH, dicyclohexylcarbodiimide and a catalytic amount of 4-dimethylaminopyridine in dichloromethane (Figure 1) (Li et al, 2006). After removal of dicyclohexylurea, the compounds were purified by column chromatography.…”

Section: Synthesis Of Dithiolethione Derivatives S-diclofenac S-sulimentioning

confidence: 99%

“…Following gelation, explants were incubated in endothelial growth medium (EGM) þ 2% FCS in the presence or absence of a dose range of the indicated treatment agents or the comparable concentration of vehicle at 371C and 5% CO 2 . The selection of treatment agent concentrations used in explant and other in vitro cell assays was based upon data obtained from in vivo experiments (Li et al, 2006). Maximum cell migration through the matrix was measured following 7 days of incubation.…”

Section: Explant Invasion Assaymentioning

confidence: 99%

“…The above observations led us to investigate the effects of a novel class of dithiolethione-modified anti-inflammatory drugs (Li et al, 2006) on angiogenic responses in vascular cells. Unlike the unmodified drugs, we found that dithiolethione-modified S-nonsteroidal anti-inflammatory drug (NSAIDs) and S-valproate demonstrated significant antiangiogenic activities, inhibiting endothelial cell proliferation and vascular cell outgrowth and invasion of extracellular matrix under wound healing as well as tumor-driven conditions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Isenberg

Jia

Field

et al. 2007

British J Pharmacology

View full text Add to dashboard Cite

Background and purpose: Angiogenesis involves multiple signaling pathways that must be considered when developing agents to modulate pathological angiogenesis. Because both cyclooxygenase inhibitors and dithioles have demonstrated antiangiogenic properties, we investigated the activities of a new class of anti-inflammatory drugs containing dithiolethione moieties (S-NSAIDs) and S-valproate. Experimental approach: Anti-angiogenic activities of S-NSAIDS, S-valproate, and the respective parent compounds were assessed using umbilical vein endothelial cells, muscle and tumor tissue explant angiogenesis assays, and developmental angiogenesis in Fli:EGFP transgenic zebrafish embryos. Key results: Dithiolethione derivatives of diclofenac, valproate, and sulindac inhibited endothelial cell proliferation and induced Ser 78 phosphorylation of hsp27, a known molecular target of anti-angiogenic signaling. The parent drugs lacked this activity, but dithiolethiones were active at comparable concentrations. Although dithiolethiones can potentially release hydrogen sulphide, NaSH did not reproduce some activities of the S-NSAIDs, indicating that the dithioles regulate angiogenesis through mechanisms other than release of H 2 S. In contrast to the parent drugs, S-NSAIDs, S-valproate, NaSH, and dithiolethiones were potent inhibitors of angiogenic responses in muscle and HT29 tumor explants assessed by 3-dimensional collagen matrix assays. Dithiolethiones and valproic acid were also potent inhibitors of developmental angiogenesis in zebrafish embryos, but the S-NSAIDs, remarkably, lacked this activity. Conclusions and implication: S-NSAIDs and S-valproate have potent anti-angiogenic activities mediated by their dithiole moieties. The novel properties of S-NSAIDs and S-valproate to inhibit pathological versus developmental angiogenesis suggest that these agents may have a role in cancer treatment.

show abstract

Section: Synthesis Of Dithiolethione Derivatives S-diclofenac S-sulimentioning

confidence: 99%

Section: Explant Invasion Assaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Isenberg

Jia

Field

et al. 2007

British J Pharmacology

View full text Add to dashboard Cite

show abstract

“…For example, Sdiclofenac has an H 2 S-releasing diothiol-thione moiety attached by an ester linkage to the parent drug. 77 With the emergence of improved pharmacological tools and the increased interest in H 2 S, the next few years should provide a greater understanding of the physiological roles of H 2 S. Like NO, H 2 S is almost certainly an agent with multiple mechanisms and sites of action. Elucidation of these will help to reveal the physiological significance and potential for medical exploitation of this intriguing and surprisingly complex gaseous mediator.…”

Section: Future Research Perspectivesmentioning

confidence: 99%

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)

Elsey

Fowkes

Baxter

2010

Cell Biochemistry & Function

138

View full text Add to dashboard Cite

Since the discovery of endogenously-produced hydrogen sulfide (H 2 S) in various tissues, there has been an explosion of interest in H 2 S as a biological mediator alongside other gaseous mediators, nitric oxide and carbon monoxide. The identification of enzymeregulated H 2 S synthetic pathways in the cardiovascular system has led to a number of studies examining specific regulatory actions of H 2 S. We review evidence showing that endogenously-generated and exogenously-administered H 2 S exerts a wide range of actions in vascular and myocardial cells including vasodilator/vasoconstrictor effects via modification of the smooth muscle tone, induction of apoptosis and anti-proliferative responses in the smooth muscle cells, angiogenic actions, effects relevant to inflammation and shock, and cytoprotection in models of myocardial ischemia-reperfusion injury. Several molecular mechanisms of action of H 2 S have been described. These include interactions of H 2 S with NO, redox regulation of multiple signaling proteins and regulation of K ATP channel opening. The gaps in our current understanding of precise mechanisms, the absence of selective pharmacological tools and the limited availability of H 2 S measurement techniques for living tissues, leave many questions about physiological and pathophysiological roles of H 2 S unanswered at present. Nevertheless, this area of investigation is advancing rapidly. We believe H 2 S holds promise as an endogenous mediator controlling a wide range of cardiovascular cell functions and integrated responses under both physiological and pathological conditions and may be amenable to therapeutic manipulation.

show abstract

“…One cannot exclude the possibility that the reduced cytokine expression/production occurred, at least in part, as a consequence of the reduced gastric injury, though H 2 S has been shown to reduce pro-inflammatory cytokine expression/synthesis in other in vivo models, including colitis [9,11,12].…”

mentioning

confidence: 99%

Hydrogen Sulfide: A Rescue Molecule for Mucosal Defence and Repair

Wallace

2012

Dig Dis Sci

View full text Add to dashboard Cite

Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative

Cited by 312 publications

References 33 publications

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)

Hydrogen Sulfide: A Rescue Molecule for Mucosal Defence and Repair

Contact Info

Product

Resources

About

Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative

Cited by 312 publications

References 33 publications

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Modulation of angiogenesis by dithiolethione‐modified NSAIDs and valproic acid

Regulation of cardiovascular cell function by hydrogen sulfide (H2S)

Hydrogen Sulfide: A Rescue Molecule for Mucosal Defence and Repair

Contact Info

Product

Resources

About

Regulation of cardiovascular cell function by hydrogen sulfide (H₂S)