Biologic evaluation of curcumin and structural derivatives in cancer chemoprevention model systems.

Curcumin is a natural product widely used as a spice in food. It has been shown to inhibit cyclooxygenase (COX)-1 and -2 and to suppress lipopolysaccharide-induced COX-2 and iNOS gene expression. In the present study, curcumin and 22 of its derivatives were evaluated for their chemopreventive potential.

Fluoride curcumin derivatives: new mitochondrial uncoupling agents.

The mitochondrial effects of two fluoride curcumin derivatives were studied. They induced the collapse of mitochondrial membrane potential (DeltaPsi), increased mitochondrial respiration, and decreased O(2)*- production and promoted Ca(2+) release. These effects were reversed by the recoupling agent 6-Ketocholestanol, but not by cyclosporin A, an inhibitor of the permeability transition pore (PTP), suggesting that these compounds act as uncoupling agents.

Effects of curcumin and curcumin derivatives on mitochondrial permeability transition pore.

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a natural compound with antiproliferative properties. Recent studies suggest that these properties might be due to the ability of curcumin to induce apoptosis in tumor cells by increasing the permeability of the mitochondrial membrane. In the present study, we confirm these observations and provide a molecular mechanism for the action of curcumin in rat liver mitochondria.

[3H]BHDP as a novel and selective ligand for sigma1 receptors in liver mitochondria and brain synaptosomes of the rat.

The binding profile of [(3)H]BHDP ([(3)H]N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine) was evaluated. [(3)H]BHDP labelled a single class of binding sites with high affinity (K(d)=2-3 nM) in rat liver mitochondria and synaptic membranes. The pharmacological characterization of these sites using sigma reference compounds revealed that these sites are sigma receptors and, more particularly, sigma1 receptors.

Dual effect of ebselen on mitochondrial permeability transition.

This study reports an investigation on the effect of the seleno-organic compound ebselen on rat liver mitochondria. We show that low concentrations of ebselen induced an increase in rat liver mitochondrial membrane permeability, resulting in swelling and loss of membrane potential. These effects were mediated by the opening of the permeability transition pore.

Curcumin induces the mitochondrial permeability transition pore mediated by membrane protein thiol oxidation.

Curcumin is a natural compound showing antiproliferative properties. Recent studies suggest that these properties might be due to its ability to induce apoptosis in tumor cells. As mitochondria play a pivotal role in the induction of the apoptotic process, we analyzed the effect of curcumin on mitochondrial function.

NO-Mediated aromatic nitration during decomposition of phenolic S-nitrosothiols in non-aqueous aerobic medium.

Five novel S-nitrosothiol compounds (6-10) derived from L-cysteine were generated in solution and their decomposition rate was followed by UV spectroscopy. In acetonitrile, compounds 9 and 10 were the most stable of this series with a half-life of 24 h. The final organic decomposition products of the five S-nitrosothiols were also analysed.

[(3)H]-trimetazidine mitochondrial binding sites: regulation by cations, effect of trimetazidine derivatives and other agents and interaction with an endogenous substance.

Trimetazidine, an antiischaemic drug, has been shown to restore impaired mitochondrial functions. Specific binding sites for [(3)H]-trimetazidine have been previously detected in liver mitochondria. In the present study we confirm this observation and provide additional evidence for the involvement of these sites in the pharmacological effects of the drug.

Novel donors of nitric oxide derived of S-nitrosocysteine possessing antioxidant activities.

Novel S-nitrosothiols possessing a phenolic function were investigated as nitric oxide (NO) donors. A study of NO release from these derivatives was carried out by electron spin resonance (ESR). All compounds gave rise to a characteristic three-line ESR signal in the presence of the complex [Fe(II)(MGD)2], revealing the formation of the complex [Fe(II)(MGD)2(NO)].

Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants.

Twenty-five compounds (trimetazidine derivatives and other compounds, mostly having a free phenolic group) were examined for their radical scavenging and antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl) as a measure of radical scavenging capacity was assessed by two parameters, namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z, a kinetic parameter proposed here and derived from initial second-order rate constants and antioxidant/DPPH ratios. Antioxidant activities were determined by the inhibition of lipid peroxidation and albumin oxidation.

Curcumin and curcumin derivatives inhibit Tat-mediated transactivation of type 1 human immunodeficiency virus long terminal repeat.

The transcription of HIV1 provirus is regulated by both cellular and viral factors. Various evidence suggests that Tat protein secreted by HIV1-infected cells may have additional action in the pathogenesis of AIDS because of its ability to also be taken up by non-infected cells. Curcumin [diferuloylmethane or 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione] is the yellow pigment in turmeric Curcuma longa (Linn).

Protective effects of the lipophilic redox conjugate tocopheryl succinyl-ethyl ferulate on HIV replication.

Previously, we demonstrated that ferulate ethyl and tocopherol reduced HIV replication. In this study, we investigate whether the conjugation of both compounds (O-tocopheryl succinyl O-ethyl ferulate) can increase HIV inhibition. We show here for the first time that O-tocopheryl succinyl O-ethyl ferulate inhibits 80% of HIV replication (HIV-1 acute infection and HIV transmission), inhibits cell lipoperoxidation and prevents cellular glutathione consumption.

[Thionitrites as potent donors of nitric oxide: example of S-nitroso- and S,S'-dinitroso-dihydrolipoic acids].

Until recently, nitric oxide (NO.) was considered as a toxic radical, but it appears now as an essential messenger implicated in a wide range of biological processes, including immune system, cardiovascular system, and nervous system. An aspect of NO.

[Substituted methoxyphenol with antioxidative activity: correlation between physicochemical and biological results].

Guaiacol moiety has been found in antiinflammatory compounds present in traditional african or chinese medicine. As the activity of these products could be due to reactions with the reactive oxygen species (ROS) or enzymes involved in the inflammatory reaction, a comparative study has been done between biological and physico-chemical investigations. Antioxidant properties of six guaiacol derivatives were measured in vitro by the inhibition of cyclooxygenase activities in human platelets and of the release of ROS by human polymorphonuclear leucocytes (PMNs).

[Effect of the liposolubility of free radical scavengers on the production of antigen P24 from a HIV infected monocytic cell line].

A large body of evidence indicates that AIDS may be the consequence of a virus-induced antioxidant deficiency and implicates reactive oxygen species (ROS) in the pathogenesis of HIV infection. The high level of antigenic acid and cytokines activities in AIDS results in the production of superoxides (O2-), hydrogen peroxide (H202) and hydroxyl radicals (OH). HIV-infected T cells display low levels of SOD, catalase, thioredoxin and glutatione peroxidase rendering them susceptible to undergo apoptosis.

Synthesis and nematocidal activity of arylmercaptovinyltetrahydropyrimidines.

A set of mercaptovinyl tetrahydropyrimidines was synthesized in good yields by lithiation of 1,2-dimethyltetrahydropyrimidine with n-butyl lithium in tetrahydrofurane, followed by condensation with aromatic thioesters. Against three nematode genera, anthelminthic screening shows little activity; 2b and 2d were the most potent against Molinema dessetae.