Synthesis of 1,2,4-Oxadiazin-5(6)-One Derivatives and Their Biological Investigation as Monoamine Oxidase Inhibitors.

Monoamine oxidase (MAO) plays a key role in the pathogenesis of central nervous system disorders, and MAO inhibitors have been used in the treatment of depression and Parkinson's disease. In the search for new classes of MAO inhibitors, the present study investigated a series of 1,2,4-oxadiazin-5(6)-one derivatives. This study provides the first optimization of the reaction conditions for the condensation of amidoximes with alkyl 2-halocarboxylates to yield the desired 1,2,4-oxadiazin-5(6)-ones.

Hematoxylin, an Alternative Substrate of Tyrosinase.

Mushroom tyrosinase from (TYR) is often used during the development of tyrosinase inhibitors for medicinal and cosmetic purposes. In the search for novel tyrosinase inhibitors, this study identified hematoxylin as an alternative substrate for TYR. The interaction of hematoxylin with TYR was investigated through spectrophotometric and chromatographic analyses.

Synthesis and evaluation of 3-hydroxyquinolin-2(1H)-one derivatives as inhibitors of tyrosinase.

The tyrosinase (TYR) enzyme catalyses sequential reactions in the melanogenesis pathway: l-tyrosine is oxidised to yield L-3,4-dihydroxyphenylalanine (l-dopa), which in turn is converted to dopaquinone. These two reactions are the first two steps of melanin biosynthesis and are rate limiting. The accumulation or overproduction of melanin may cause skin hyperpigmentation and inhibitors of TYR are thus of interest to the cosmeceutical industry.

A Multitarget Approach against Neuroinflammation: Alkyl Substituted Coumarins as Inhibitors of Enzymes Involved in Neurodegeneration.

Neurodegenerative disorders (NDs) include a large range of diseases characterized by neural dysfunction with a multifactorial etiology. The most common NDs are Alzheimer's disease and Parkinson's disease, in which cholinergic and dopaminergic systems are impaired, respectively. Despite different brain regions being affected, oxidative stress and inflammation were found to be common triggers in the pathogenesis and progression of both diseases.

The evaluation of isatin analogues as inhibitors of monoamine oxidase.

The small molecule, isatin, is a well-known reversible inhibitor of the monoamine oxidase (MAO) enzymes with IC values of 12.3 and 4.86 μM for MAO-A and MAO-B, respectively.

Monoamine oxidase inhibition properties of 2,1-benzisoxazole derivatives.

Monoamine oxidase (MAO) are flavoenzymes that metabolize neurotransmitter, dietary and xenobiotic amines to their corresponding aldehydes with the production of hydrogen peroxide. Two isoforms, MAO-A and MAO-B, are expressed in humans and mammals, and display different substrate and inhibitor specificities as well as different physiological roles. MAO inhibitors are of much therapeutic value and are used for the treatment of neuropsychiatric and neurodegenerative disorders such as depression, anxiety disorders, and Parkinson's disease.

Synthesis and in vitro antiprotozoal evaluation of novel metronidazole-Schiff base hybrids.

Herein we report the synthesis of 21 novel small molecules inspired by metronidazole and Schiff base compounds. The compounds were evaluated against Trichomonas vaginalis and cross-screened against other pathogenic protozoans of clinical relevance. Most of these compounds were potent against T.

Coumarin-Based Dual Inhibitors of Human Carbonic Anhydrases and Monoamine Oxidases Featuring Amino Acyl and ()-Dipeptidyl Appendages: In Vitro and Computational Studies.

The involvement of human carbonic anhydrase (hCA) IX/XII in the pathogenesis and progression of many types of cancer is well acknowledged, and more recently human monoamine oxidases (hMAOs) A and B have been found important contributors to tumor development and aggressiveness. With a view of an enzymatic dual-blockade approach, in this investigation, new coumarin-based amino acyl and ()-dipeptidyl derivatives were synthesized and firstly evaluated in vitro for inhibitory activity and selectivity against membrane-bound and cytosolic hCAs (hCA IX/XII over hCA I/II), as well as the hMAOs, to estimate their potential as anticancer agents. design of peptide-coumarin conjugates was subsequently carried out and involved the combination of the widely explored coumarin nucleus with the unique biophysical and structural properties of native or modified peptides.

Resveratrol Analogues as Dual Inhibitors of Monoamine Oxidase B and Carbonic Anhydrase VII: A New Multi-Target Combination for Neurodegenerative Diseases?

Neurodegenerative diseases (NDs) are described as multifactorial and progressive syndromes with compromised cognitive and behavioral functions. The multi-target-directed ligand (MTDL) strategy is a promising paradigm in drug discovery, potentially leading to new opportunities to manage such complex diseases. Here, we studied the dual ability of a set of resveratrol (RSV) analogs to inhibit two important targets involved in neurodegeneration.

The inhibition of monoamine oxidase by 2H-1,4-benzothiazin-3(4H)-ones.

Monoamine oxidase (MAO) plays an important role in psychiatric and neurological disorders, such as depression and Parkinson's disease. As a result, MAO represents a key target for developing drugs to treat these conditions. The present study aimed to synthesise and discover compounds that inhibit the MAO enzymes and which may be relevant to the treatment of neurological disorders.

New β-arylchalcogeno amines with procognitive properties targeting Carbonic Anhydrases and Monoamine Oxidases.

Cognitive deficits are enduring and disabling symptoms for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. In this study, we reported the synthesis of β-arylchalcogeno amines bearing sulfurated, selenated, and tellurated moieties (2-4) which are structurally related to amphetamine with good activation properties for Carbonic Anhydrases (CAs) isoforms present in the cortical and hippocampal brain structures (hCA IV and hCA XIV). In addition, these compounds showed selective inhibition against the Monoamine oxidase (MAO) A isoform.

Isatoic anhydrides as novel inhibitors of monoamine oxidase.

The monoamine oxidase (MAO) enzymes metabolise neurotransmitter amines in the central and peripheral tissues, and thereby contribute to the regulation of neurotransmission. Inhibitors of MAO modulate the levels of neurotransmitters in the central nervous system, and have been used for several decades for the treatment of depression and Parkinson's disease, while potential new therapeutic applications in other diseases such as prostate cancer and heart failure may exist. In the interest of discovering new classes of chemical compounds that potently inhibit the MAOs, the present study synthesises a series of ten isatoic anhydrides and evaluates their potential as in vitro inhibitors of human MAO-A and MAO-B.

An updated patent review on monoamine oxidase (MAO) inhibitors.

Introduction: Monoamine oxidase (MAO) inhibitors are currently used as antidepressants (selective MAO-A inhibitors) or as co-adjuvants for neurodegenerative diseases (selective MAO-B inhibitors). The research within this field is attracting attention due to their crucial role in the modulation of brain functions, mood, and cognitive activity, and monoamine catabolism.

Areas Covered: MAO inhibitors (2018-2021) are discussed according to their chemotypes.

The evaluation of N-propargylamine-2-aminotetralin as an inhibitor of monoamine oxidase.

Monoamine oxidase B (MAO-B) inhibitors are established therapy for Parkinson's disease and act, in part, by blocking the MAO-catalysed metabolism of dopamine in the brain. Two propargylamine-containing MAO-B inhibitors, selegiline [(R)-deprenyl] and rasagiline, are currently used in the clinic for this purpose. These compounds are mechanism-based inactivators and, after oxidative activation, form covalent adducts with the FAD co-factor.

Coumarin derivatives as inhibitors of d-amino acid oxidase and monoamine oxidase.

d-Amino acid oxidase (DAAO) oxidises d-amino acids to ultimately produce the corresponding α-keto acids. The DAAO substrate, d-serine, is a co-agonist at NMDA receptors, while NMDA receptor hypo-function has been implicated in the pathophysiology of schizophrenia. Through the modulation of d-serine levels, the inhibition of DAAO represents a strategy to increase NMDA receptor function, and thus a potential treatment for schizophrenia.

Phenothiazine, anthraquinone and related tricyclic derivatives as inhibitors of monoamine oxidase.

Inhibitors of the monoamine oxidase (MAO) enzymes are important agents for the treatment of central nervous system disorders and have established roles in the therapy of neuropsychiatric diseases such as depression and in the neurodegenerative disorder, Parkinson's disease. A number of good potency MAO inhibitors consist of tricyclic ring systems as exemplified by the structures of harmine and the phenothiazine compound methylene blue. In an attempt to discover novel MAO inhibitors, 30 phenothiazine, anthraquinone and related tricyclic derivatives were selected and evaluated as potential inhibitors of human MAO-A and MAO-B.

Betulin, a Newly Characterized Compound in Bark, Is a Multi-Target Protein Kinase Inhibitor.

The purpose of this work is to investigate the protein kinase inhibitory activity of constituents from stem bark. Column chromatography and NMR spectroscopy were used to purify and characterize betulin from an ethyl acetate soluble fraction of acacia bark. Betulin, a known inducer of apoptosis, was screened against a panel of 16 disease-related protein kinases.

The inhibition of catechol O-methyltransferase and monoamine oxidase by tetralone and indanone derivatives substituted with the nitrocatechol moiety.

The enzymes, catechol O-methyltransferase (COMT) and monoamine oxidase (MAO) are important drug targets, and inhibitors of these enzymes are established therapy for symptomatic Parkinson's disease (PD). COMT inhibitors enhance the bioavailability of levodopa to the brain, and therefore are combined with levodopa for the treatment of motor fluctuations in PD. Inhibitors of the MAO-B isoform, in turn, are used as monotherapy or in conjunction with levodopa in PD, and function by reducing the central degradation of dopamine.

Methylene blue analogues: In vitro antimicrobial minimum inhibitory concentrations and in silico pharmacophore modelling.

It has been shown that methylene blue has antimicrobial properties although few studies have determined its minimum inhibitory concentration (MIC), which is the gold standard used to measure antimicrobial activity. The exact antimicrobial mode of action of methylene blue is still unclear and to our knowledge no pharmacophore model has yet been created to investigate methylene blue's mode of action. The aim of this study was to determine the MIC of methylene blue and a number of its analogous against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Salmonella enterica and Candida albicans, and to use these data to develop and validate a common feature pharmacophore model.

The evaluation of 1-tetralone and 4-chromanone derivatives as inhibitors of monoamine oxidase.

Monoamine oxidase (MAO) is of much clinical relevance, and inhibitors of this enzyme are used in the treatment for neuropsychiatric and neurodegenerative disorders such as depression and Parkinson's disease. The present study synthesises and evaluates the MAO inhibition properties of a series of 33 1-tetralone and 4-chromanone derivatives in an attempt to discover high-potency compounds and to expand on the structure-activity relationships of MAO inhibition by these classes. Among these series, eight submicromolar MAO-A inhibitors and 28 submicromolar MAO-B inhibitors are reported, with all compounds acting as specific inhibitors of the MAO-B isoform.

Evaluation of nitrocatechol chalcone and pyrazoline derivatives as inhibitors of catechol-O-methyltransferase and monoamine oxidase.

Literature reports that chalcones inhibit the monoamine oxidase (MAO) enzymes, mostly with specificity for the MAO-B isoform, while nitrocatechol compounds are established inhibitors of catechol-O-methyltransferase (COMT). Based on this, nitrocatechol derivatives of chalcone have been proposed to represent dual-target-directed compounds that may inhibit both MAO-B and COMT. Both these enzymes play key roles in the metabolism of dopamine and levodopa, and inhibitors are thus relevant to the treatment of Parkinson's disease.

Synthesis and evaluation of 7-azaindole derivatives bearing benzocycloalkanone motifs as protein kinase inhibitors.

Protein kinases are important drug targets, especially in the area of oncology. This paper reports the synthesis and biological evaluation of new 7-azaindole derivatives bearing benzocycloalkanone motifs as potential protein kinase inhibitors. Four compounds 8g, 8h, 8i, and 8l were discovered to inhibit cyclin-dependent kinase 9 (CDK9/CyclinT) and/or Haspin kinase in the micromolar to nanomolar range.

Design, synthesis and evaluation of 3-hydroxypyridin-4-ones as inhibitors of catechol-O-methyltransferase.

The most effective treatment of Parkinson's disease is restoring central dopamine levels with levodopa, the metabolic precursor of dopamine. However, due to extensive peripheral metabolism by aromatic L-amino acid decarboxylase and catechol-O-methyltransferase (COMT), only a fraction of the levodopa dose reaches the brain unchanged. Thus, by preventing levodopa metabolism and increasing the availability of levodopa for uptake into the brain, the inhibition of COMT would be beneficial in Parkinson's disease.