Dicoumarol derivatives: Green synthesis and molecular modelling studies of their anti-LOX activity.

Dicoumarol derivatives were synthesized in the InCl catalyzed pseudo three-component reactions of 4-hydroxycoumarin with aromatic aldehydes in excellent yields. The reactions were performed in water under microwave irradiation. All synthesized compounds were characterized using NMR, IR, and UV-Vis spectroscopy, as well as with TD-DFT.

Synthesis and Biological Evaluation of Novel Hybrid Molecules Containing Purine, Coumarin and Isoxazoline or Isoxazole Moieties.

Introduction: The 1,3-dipolar cycloaddition reactions of nitrile oxides formed (in the presence of NCS and EtN) from the oximes of (purin-9-yl)acetaldehyde or (coumarinyloxy)acetaldehyde with allyloxycoumarins or 9-allylpurines, respectively resulted in 3,5-disubstituted isoxazolines. The similar reactions of propargyloxycoumarins or 9-propargylpurines led to 3,5-disubstituted isoxazoles by treatment with PIDA and catalytic amount of TFA.

Methods: The new compounds were tested as antioxidant agents and inhibitors of soybean lipoxygenase LO, AChE and MAO-B.

Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins.

A series of 3-acylhydrazono-4-hydroxycoumarins were synthesized via condensation of 3-acetyl-4-hydroxycoumarin with appropriate hydrazides. The structures of the newly-synthesized compounds were characterized by spectral and elememental analysis or HRMS measurements. Their antioxidant properties were evaluated by using scavenging effects on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical as well as inhibition of lipid peroxidation.

CholesteroNitrones for Stroke.

This study describes CholesteroNitrone 2 as an antioxidant and neuroprotective agent against ischemic injury. Neuroprotection was assessed using in vitro and in vivo experimental ischemia models. The compound significantly increased cell viability, induced neuroprotection following ischemic reperfusion, and decreased neurological deficit scores in treated animals, supporting the next preclinical studies as a potential agent for the treatment of stroke.

Simple chalcones and bis-chalcones ethers as possible pleiotropic agents.

The synthesis, the antioxidative properties and the lipoxygenase (LOX) and acetylcholinesterase (AChE) inhibition of a number of 4-hydroxy-chalcones diversely substituted as well as of a series of bis-chalcones ether derivatives are reported. The chalcones derivatives were readily produced using a Claisen-Schmidt condensation in a ultra sound bath in good yields. The structures of the synthesized compounds were confirmed by spectral and elemental analysis.

Purine homo-N-nucleoside+coumarin hybrids as pleiotropic agents for the potential treatment of Alzheimer's disease.

Aim: Due to the complex nature of Alzheimer's disease, there is a renewed search for pleiotropic agents.

Results: Purine+coumarin hybrids have been synthesized and tested for the potential treatment of Alzheimer's disease. Hybrids 6, 4a-b, 14c and 14e inhibit significantly soybean lipoxygenase, whereas derivatives 14b, c and 20a present antioxidative/lipoxygenase inhibition activities.

Synthesis and biological evaluation of modified purine homo-N-nucleosides containing pyrazole or 2-pyrazoline moiety.

9-Substituted (pyrazol-5-yl)methyl- or (2-pyrazolin-5-yl)methyl-9H-purines were synthesized from 9-allyl-6-chloro-9H-purine through the 1,3-dipolar cycloaddition reaction with nitrile imines, prepared in situ from the corresponding hydrazone and NBS/Et3N under MW or from hydrazinoylchloride and Et3N under reflux. The coupling of new 6-chloropurines with amines in H2O under microwaves resulted quantitatively to modified pyrazol-5-yl- or 2-pyrazolin-5-yl adenine homo-N-nucleosides. The new compounds were tested in vitro for their ability to: (i) interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH), (ii) inhibit lipid peroxidation, (iii) inhibit the activity of soybean lipoxygenase, (iv) inhibit in vitro thrombin and for (v) their antiproliferative and cytotoxic activity.

Synthesis of purine homo-N-nucleosides modified with coumarins as free radicals scavengers.

Cross metathesis (CM) of 9-butenylpurines with 4-butenyloxycoumarin in the presence of Grubbs 2nd generation catalyst under MW irradiation resulted to conjugated compounds containing homo-N-nucleosides and coumarins. Analogous derivatives received by the CM reaction of 9-butenyl-6-piperidinylpurine with 6- or 7-butenyloxycoumarins, allyloxycoumarins or coumarinyl acrylate. These compounds were tested in vitro for their antioxidant activity and they present significant scavenging activity.

Synthesis and biological evaluation of (2,5-dihydro-1H-pyrrol-1-yl)-2H-chromen-2-ones as free radical scavengers.

The allylation of aminocoumarins in the presence of excess of anhydrous K(2)CO(3) and allyl bromide to diallylaminocoumarins is described. The Ring Closing Metathesis reaction of the later with the Grubbs' 1rst generation catalyst under reflux or MW irradiation has resulted mainly to (2,5-dihydro-1H-pyrrol-1-yl)coumarins and (1H-pyrrol-1-yl)coumarins. The new compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase LO and (v) to scavenge hydroxyl radicals.

Synthesis and biological evaluation of fused oxepinocoumarins as free radicals scavengers.

Some fused dihydrooxepino[f]-, [g]-, and [h]coumarins were obtained from the ring-closing metathesis of the corresponding o-allyl-allyloxycoumarins under the treatment with the first generation Grubbs' catalyst. These compounds were tested in vitro for their antioxidant activity, and they present significant scavenging activity. They were also showed to inhibit in vitro soybean lipoxygenase.

One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schiff bases and pyrimido[1,2-a]benzimidazol-3(4H)-ones.

The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts.

1,5-Benzoxazepines vs 1,5-benzodiazepines. one-pot microwave-assisted synthesis and evaluation for antioxidant activity and lipid peroxidation inhibition.

Amino-1,5-benzoxazepines 2 and 5 and hydroxyl-1,5-benzodiazepines 3 and 6 have been synthesized in one-pot solvent-free conditions from 2,3-diaminophenol and ketones through microwave assisted acid catalysis, the benzoxazepine/benzodiazepine ratio depending on the R(1) and R(3) aryl substituents. The otherwise inaccessible and unknown 2,2-dimethyl-4-aryl-1,5-benzodiazepines 8 were also prepared in an analogous manner. The reaction mechanism was investigated by means of DFT calculations.

Synthesis of modified homo-N-nucleosides from the reactions of mesityl nitrile oxide with 9-allylpurines and their influence on lipid peroxidation and thrombin inhibition.

9-(3-Mesityl-4,5-dihydroisoxazol-5-yl) homo-N-nucleosides were prepared from the 1,3-dipolar cycloaddition reactions of mesityl nitrile oxide with 9-allyl derivatives of 6-chloropurine, 6-piperidinylpurine, 6-morpholinylpurine, 6-pyrrolidinylpurine, and 6-N,N-dibenzoyladenine. The new compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase, and (v) to inhibit in vitro thrombin. Most of them found to be potent thrombin inhibitors and to inhibit in vitro lipid peroxidation.

Synthesis and anti-inflammatory evaluation of novel angularly or linearly fused coumarins.

Angular [7,8]-fused coumarins were obtained from the reaction of [2,3]-fused phenols with DMAD and PPh(3), while linear [6,7]-fused coumarins were formed from the analogous reaction of [3,4]-fused phenols with DMAD and PPh(3). These compounds were tested in vitro for antioxidant activity and they found to present significant scavenging activity. In parallel, these new compounds were evaluated in vivo for anti-inflammatory activity and they found to inhibit the carrageenin-induced paw edema (34-65%).

Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts.

In the present work a series of novel coumarin-3-carboxamides and their hybrids with the alpha-lipoic acid were designed, synthesized and tested as potent antioxidant and anti-inflammatory agents. The new compounds were evaluated for their antioxidant activity, their activity to inhibit in vitro lipoxygenase and their in vivo anti-inflammatory activity. In general, the derivatives were generally found to present antioxidant and anti-inflammatory activities.

Synthesis of hydroxycoumarins and hydroxybenzo[f]- or [h]coumarins as lipid peroxidation inhibitors.

Substituted hydroxycoumarins and 7- or 8-hydroxybenzo[f]coumarins were prepared by the treatment of phenols and naphthalenediols, respectively, with malic acid and H(2)SO(4) under microwave irradiation. 7- or 8-Hydroxybenzo[f]coumarins and 6-hydroxybenzo[h]coumarin were synthesized by the reaction of naphthalenediols with ethylpropiolate in the presence of ZnCl(2) in refluxing dioxane. The compounds were tested in vitro for their ability: (i) to interact with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) stable free radical, (ii) to inhibit lipid peroxidation, (iii) to scavenge the superoxide anion, (iv) to inhibit the activity of soybean lipoxygenase and (v) to inhibit in vivo the carrageenin-induced rat paw edema.

Synthesis and biological evaluation of novel angular fused Pyrrolocoumarins.

Angular pyrrolocoumarins were synthesized from the reaction of 4-hydroxyindole or 5-hydroxyindole with DMAD and PPh(3) and were tested for anti-inflammatory and antioxidant activity. These compounds significantly inhibited the carrageenin-induced paw edema (60.5%-73.

Design and synthesis of novel quinolinone-3-aminoamides and their alpha-lipoic acid adducts as antioxidant and anti-inflammatory agents.

A series of N-substituted-quinolinone-3-aminoamides and their hybrids containing the alpha-lipoic acid functionality were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity. The new compounds were evaluated for their antioxidant activity and for their ability to inhibit in vitro lipoxygenase as well as for their anti-inflammatory activity in vivo. In general, the derivatives were found to be potent antioxidant or anti-inflammatory agents.

Antiinflammatory and antioxidant evaluation of novel coumarin derivatives.

Several coumarin derivatives have been reported to present multiple biological activities and especially antiinflammatory/antioxidant activities. Recently the synthesis and in vivo/in vitro anti-inflammatory/antioxidant activities of several new coumarin derivatives with a 7-azomethine linkage have been reported. In the present study these derivatives were further tested for their antioxidant ability.

Synthesis and antiinflammatory activity of coumarin derivatives.

The synthesis of several coumarin Mannich bases is described. The structures of the synthesized compounds were confirmed by spectral and elemental analysis. Their lipophilicity was determined experimentally by RPTLC method.

Quantitative structure activity relationships (QSAR) of substituded (S)-phenylpiperidines as preferential dopamine autoreceptor antagonists.

A QSAR analysis for substituted (S)-phenylpiperidines as dopamine (DA) antagonists is described. The studied derivatives differ at the nitrogen substitutent (R) and at the substitutents (X) of the phenyl-ring. The analysis was done using the C-QSAR suite program (Biobyte) through the Internet.

Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities.

Several natural products with a coumarinic moiety have been reported to have multiple biological activities. It is to be expected that, in a similar way to isomeric flavonoids, coumarins might affect the formation and scavenging of reactive oxygen species (ROS) and influence processes involving free radical-mediated injury. Coumarin can reduce tissue edema and inflammation.

Synthesis and evaluation of the antioxidant and antiinflammatory activities of some benzo[l]khellactone derivatives and analogues.

Treatment of 3-hydroxy-beta-lapachone 4 with ylide 5 gave the coumarin derivative 7a, which was transformed to compounds 10-14. Compound 14 was then transformed to benzo[f]seselin 15 as well as to benzo[l]khellactones 16, 18 from which the title compounds 17, 19(I), 19(II), 20, 21(I) and 21(II) were prepared. All the tested compounds were found to interact with DPPH in a concentration and time dependent manner.

Synthesis and biological evaluation of novel coumarin derivatives with a 7-azomethine linkage.

The synthesis of several novel coumarin derivatives with a 7-azomethine linkage was carried out starting from 7-formyl-coumarin. The compounds were tested in vivo for their anti-inflammatory activity and in vitro for their antioxidant ability. Compounds 3a and 3e possess significant protection against carrageenin induced rat paw edema.

Synthesis, antioxidant and antiinflammatory activity of novel aryla-cetic and aryl-hydroxamic acids.

Four new aryl-acetic acids and the corresponding hydroxamic acids were synthesized. These compounds showed interesting interaction with the free radical 1,1-diphenyl-2-picryl-hydrazyl (DPPH), scavenging activity on .OH, inhibition of soybean lipoxygenase and a significant inhibition of carrageenin induced paw edema in rats (44.