"A patent review on arachidonic acid lipoxygenase (LOX) inhibitors for the treatment of neurodegenerative diseases (2018-present)".

Introduction: Neuroinflammation is correlated to neurodegenerative diseases like Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), Huntington Disease (HD), and Parkinson's disease (PD). A lot of recent research and patents are focused on the design and synthesis of arachidonic acid lipoxygenase (ALOX) inhibitors for the treatment of neurodegenerative diseases.

Areas Covered: The survey covers natural products, synthesis, hybrids, and assessments of biological effects in biological studies as ALOX inhibitors.

Chemical, In Cellulo, and In Silico Characterization of the Aminocholine Analogs of VG.

V-type nerve agents are exceedingly toxic chemical warfare agents that irreversibly inhibit acetylcholinesterase (AChE), leading to acetylcholine accumulation in synapses and the disruption of neurotransmission. VG or O.O-diethyl S-(diethylamino)ethyl phosphorothiolate was the first compound of this class that was synthesized.

Secondary Metabolites and Their Biological Evaluation from the Aerial Parts of Sibth. & Sm. (Asteraceae).

Phytochemical investigation of Sibth. & Sm. resulted in the isolation of twenty-two natural products: eleven sesquiterpene lactones, artemorin (), tamirin (), tanachin (), reynosin (), baynol C (), desacetyl-β-cyclopyrethrosin (), 1β-hydroxy-4α-methoxy-5α,7α,6β-eudesm-11(13)-en-6,12-olide (), 1β,4α,6α-trihydroxyeudesm-11-en-8α,12-olide (), 1β-hydroxy-arbusculin A (), methyl-1β,4α,6α-trihydroxy-5α,7αH-eudesm-11(13)-en-12-oate () and methyl-1β,6α,8α-trihydroxy-5α,7αH-eudesma-4(15),11(13)-dien-12-oate (); one lignan, pinoresinol (); one norisoprenoid, loliolide (); six flavonoids (four genins and two glycosides), hispidulin (), nepetin (), jaceosidin (), eriodictyol (), eriodictyol-3'-O-β-D-glucoside () and eriodictyol-7-O-β-D-glucuronide (); and three phenolic derivatives (one phenolic acid and two phenolic glucosides), protocatechuic acid (), arbutin () and nebrodenside A ().

Approaches for the discovery of cinnamic acid derivatives with anticancer potential.

Introduction: Cinnamic acid is a privileged scaffold for the design of biologically active compounds with putative anticancer potential, following different synthetic methodologies and procedures. Since there is a need for the production of potent anticancer, cinnamate moiety can significantly contribute in the design of new and more active anticancer agents.

Areas Covered: In this review, the authors provide a review on the synthetic approaches for the discovery of cinnamic acid derivatives with anticancer potential.

Synthesis and Antioxidant Activity of -Benzyl-2-[4-(aryl)-1-1,2,3-triazol-1-yl]ethan-1-imine Oxides.

The synthesis, antioxidant capacity, and anti-inflammatory activity of four novel -benzyl-2-[4-(aryl)-1-1,2,3-triazol-1-yl]ethan-1-imine oxides - are reported herein. The nitrones - were tested for their antioxidant properties and their ability to inhibit soybean lipoxygenase (LOX). Four diverse antioxidant tests were used for in vitro antioxidant assays, namely, interaction with the stable free radical DPPH (1,1-diphenyl-2-picrylhydrazyl radical) as well as with the water-soluble azo compound AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride), competition with DMSO for hydroxyl radicals, and the scavenging of cationic radical ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) radical cation).

Pharmacochemical Study of Multitarget Amino Acids' Hybrids: Design, Synthesis, , and Studies.

Introduction: Neuro-inflammation is a complex phenomenon resulting in several disorders. ALOX-5, COX-2, pro-inflammatory enzymes, and amino acid neurotransmitters are tightly correlated to neuro-inflammatory pathologies. Developing drugs that interfere with these targets will offer treatment for various diseases.

Synthesis, antioxidant and neuroprotective analysis of diversely functionalized α-aryl-N-alkyl nitrones as potential agents for ischemic stroke therapy.

Herein, we report the synthesis, antioxidant and biological evaluation of 32 monosubstituted α-arylnitrones derived from α-phenyl-tert-butyl nitrone (PBN) in the search for neuroprotective compounds for ischemic stroke therapy, trying to elucidate the structural patterns responsible for their neuroprotective activity. Not surprisingly, the N-tert-butyl moiety plays beneficious role in comparison to other differently N-substituted nitrone groups. It seems that electron donor substituents at the ortho position and electron withdrawing substituents at the meta position of the aryl ring induce good neuroprotective activity.

Development of Novel Pyrrole Derivatives and Their Cinnamic Hybrids as Dual COX-2/LOX Inhibitors.

Molecular hybridization has emerged as a promising approach in the treatment of diseases exhibiting multifactorial etiology. With regard to this, dual cyclooxygenase-2/lipoxygenase (COX-2/LOX) inhibitors could be considered a safe alternative to traditional non-steroidal anti-inflammatory drugs (tNSAIDs) and selective COX-2 inhibitors (coxibs) for the treatment of inflammatory conditions. Taking this into account, six novel pyrrole derivatives and pyrrole-cinnamate hybrids were developed as potential COX-2 and soybean LOX (sLOX) inhibitors with antioxidant activity.

QSAR Studies of Nitric Oxide Synthase Inhibitors.

Background: Nitric oxide is a free radical bioregulator controlling homeostasis, vasodilation, and inhibition of platelet aggregation, significantly implicated in the nervous and immune system functionality. In vivo it is produced by nitric oxide synthases (NOSs).

Objective: Overproduction of nitric oxide is linked to several inflammatory, immunological, and neurodegenerative diseases and for that, various compounds have been synthesized as inhibitors of NOSs.

Thiocarbohydrazone and Chalcone-Derived 3,4-Dihydropyrimidinethione as Lipid Peroxidation and Soybean Lipoxygenase Inhibitors.

The potential of the 4,6-diphenyl-3,4-dihydropyrimidine-2(1)-thione (abbreviated as ) and ()-'-benzylidenehydrazinecarbothiohydrazide (abbreviated as ) compounds as possible drug leads is investigated. and are synthesized in high yield of up to 97%. Their structure, binding in the active site of the LOX-1 enzyme, and their toxicity are studied via joint experimental and computational methodologies.

Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models.

Cerebral ischemia is a condition affecting an increasing number of people worldwide, and the main cause of disability. Current research focuses on the search for neuroprotective drugs for its treatment, based on the molecular targets involved in the ischemic cascade. Nitrones are potent antioxidant molecules that can reduce oxidative stress.

Exploring the Medicinal Potential of in Greek Wild-Growing Populations: Characterization of Volatile Compounds, Anti-Inflammatory and Antioxidant Activities of Leaves and Inflorescences.

Various species of the genus L. (Asteraceae) are traditionally used worldwide for wound healing against diarrhea, flatulence, and abdominal pains, as diuretic and emmenagogue agents. In the present study, the essential oils (EOs) obtained separately from the leaves and inflorescences of wild-growing Friv.

Optimizing the Distillation of Greek Oregano-Do Process Parameters Affect Bioactive Aroma Constituents and In Vitro Antioxidant Activity?

The aim of the present work was to optimize the conditions of the distillation process at a pilot scale to maximize the yield of specific bioactive compounds of the essential oil of oregano cultivated in Greece, and subsequently to study the in vitro antioxidant activity of these oils. Steam distillation was conducted at an industrial distillery and a Face-Centered Composite (FCC) experimental design was applied by utilizing three distillation factors: time, steam pressure and temperature. Essential oil composition was determined by static headspace gas chromatography-mass spectrometry (HS-GC/MS).

Synthesis, structural characterization and study of antioxidant and anti-PrP properties of flavonoids and their rhenium(I)-tricarbonyl complexes.

This study aims at the synthesis and initial biological evaluation of novel rhenium-tricarbonyl complexes of 3,3',4',5,7-pentahydroxyflavone (quercetin), 3,7,4΄-trihydroxyflavone (resokaempferol), 5,7-dihydroxyflavone (chrysin) and 4΄,5,7-trihydroxyflavonone (naringenin) as neuroprotective and anti-PrP agents. Resokaempferol was synthesized from 2,2΄,4-trihydroxychalcone by HO/NaOH. The rhenium-tricarbonyl complexes of the type fac-[Re(CO)(Fl)(sol)] were synthesized by reacting the precursor fac-[Re(CO)(sol)] with an equimolar amount of the flavonoids (Fl) quercetin, resokaempferol, chrysin and naringenin and the solvent (sol) was methanol or water.

Synthesis and Antioxidant Properties of Novel 1,2,3-Triazole-Containing Nitrones.

Herein, we report the synthesis and antioxidant capacity of twelve novel 1,2,3-triazole-containing nitrones such as -(2-(4-aryl-1-1,2,3-triazol-1-yl)ethylidene)methanamine oxides - and -(2-(4-aryl)-1-1,2,3-triazol-1-yl)ethylidene)-2-methylpropan-2-amine oxides -, bearing an -methyl, and an -butyl substituent, respectively, at the nitrogen of the nitrone motif. Nitrones and were studied with regard to their antioxidant ability, as well as their ability to inhibit soybean lypoxygenase (LOX), and their in vitro antioxidant activity. For this, we used three different antioxidant assays, such as that featuring the interaction with the water-soluble azo compound AAPH for the inhibition of lipid peroxidation (LP), the competition with the DMSO for scavenging hydroxyl radicals, and the ABTS-decolorization assay.

Polyfunctionalized α-Phenyl-tert-butyl(benzyl)nitrones: Multifunctional Antioxidants for Stroke Treatment.

Nowadays, most stroke patients are treated exclusively with recombinant tissue plasminogen activator, a drug with serious side effects and limited therapeutic window. For this reason, and because of the known effects of oxidative stress on stroke, a more tolerable and efficient therapy for stroke is being sought that focuses on the control and scavenging of highly toxic reactive oxygen species by appropriate small molecules, such as nitrones with antioxidant properties. In this context, herein we report here the synthesis, antioxidant, and neuroprotective properties of twelve novel polyfunctionalized α-phenyl--butyl(benzyl)nitrones.

Synthesis and Antioxidant Properties of HeteroBisNitrones Derived from Benzene Dicarbaldehydes.

We report herein the synthesis and antioxidant profile of nine novel heterobisnitrones (hBNs) as new -phenyl--butylnitrone (PBN) analogues. The synthesized hBNs 1-9 were evaluated for their antioxidant activity using different in vitro techniques, while they were also tested as inhibitors of soybean LOX, as an indication of their anti-inflammatory effect. Nitrone hBN9 is the most potent antioxidant presenting higher anti-lipid peroxidation and hydroxyl radicals scavenging activities as well as higher lipoxygenase inhibition.

The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer's Disease In Vitro.

Alzheimer's disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated.

Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia-Reperfusion.

Herein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named -. The neuroprotective properties of nitrones, -, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, -, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone () and are similar to N-acetyl-L-cysteine (), a well-known antioxidant and neuroprotective agent.

-Acylated and -Alkylated 2-Aminobenzothiazoles Are Novel Agents That Suppress the Generation of Prostaglandin E.

The quest for novel agents to regulate the generation of prostaglandin E (PGE) is of high importance because this eicosanoid is a key player in inflammatory diseases. We synthesized a series of -acylated and -alkylated 2-aminobenzothiazoles and related heterocycles (benzoxazoles and benzimidazoles) and evaluated their ability to suppress the cytokine-stimulated generation of PGE in rat mesangial cells. 2-Aminobenzothiazoles, either acylated by the 3-(naphthalen-2-yl)propanoyl moiety (GK510) or -alkylated by a chain carrying a naphthalene (GK543) or a phenyl moiety (GK562) at a distance of three carbon atoms, stand out in inhibiting PGE generation, with EC values ranging from 118 nM to 177 nM.

Chemical constituents isolated from the aerial parts of (A. Braun) Boiss. (Ranunculaceae), evaluation of their antioxidant and anti-inflammatory activity and virtual screening of molecular properties and bioactivity score.

Chemical investigation of ethyl acetate extract from the aerial parts of (A.Braun) Boiss. led to the isolation of ten natural products, and their structures were identified to be: 2-deoxy-D-ribono-1,4-lactone (), 2-O-feruloyl-L-malate (), three flavonoids: quercetin 3-O--D-galactopyranoside (), quercetin 3-O-6''-(3-hydroxy-3-methyl-gloutaryl)--D-glucopyranoside () and quercetin 3-O-(2‴-caffeoylsophoroside) (), 6-O-caffeoyl-1-O--coumaroyl--D-glucopyranoside (), two ecdysteroids: 20-hydroxyecdysone () and polypodine B () and two bufadienolides: deglucohellebrin () and hellebrin (), on the basis of MS and NMR spectra.

Community Attitudes and Habits Toward Over-The-Counter Drugs: Results of a Study Conducted in Thessaloniki, Greece.

Objectives: To determine the frequency of use, sources of information, and selection criteria of Greek residents regarding over-the-counter (OTC) drugs, as well as their opinion about their dispensing in nonpharmacy settings.

Methods: This was a survey study in which an anonymous cross-sectional questionnaire was used to assess the knowledge, habits, and attitudes about OTC drugs. Data were collected from March 2017 to July 2017 in Thessaloniki, the second largest city in Greece.

Hybrids as NO Donors.

Cinnamic acid and its derivatives have been studied for a variety of biological properties, including anti-inflammatory, antioxidant, anticancer, antihypertensive, and antibacterial. Many hybrids of cinnamic derivatives with other bioactive molecules have been synthesized and evaluated as nitric oxide (NO) donors. Since NO plays a significant role in various biological processes, including vasodilation, inflammation, and neurotransmission, NO donor groups are incorporated into the structures of already-known bioactive molecules to enhance their biological properties.

Molecular investigation of artificial and natural sweeteners as potential anti-inflammatory agents.

Repurposing existing drugs, as well as natural and artificial sweeteners for novel therapeutic indications could speed up the drug discovery process since numerous associated risks and costs for drug development can be surpassed. In this study, natural and artificial sweeteners have been evaluated by and experimental studies for their potency to inhibit lipoxygenase enzyme, an enzyme participating in the inflammation pathway. A variety of different methods pinpointed that aspartame inhibits the lipoxygenase isoform 1 (LOX-1).

Investigating Potential Drug-Drug Interactions from Greek e-Prescription Data.

Background: The prevalence of potential drug-drug interactions (pDDIs) is indicative of the prevalence of actual drug-drug interactions and prescription quality. However, they are significantly understudied in Greece.

Objective: The objective of the study was to determine the prevalence of pDDIs among outpatients and identify factors associated with their occurrence.