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JournalISSN: 0009-4374

European Journal of Medicinal Chemistry

About: European Journal of Medicinal Chemistry is an academic journal. The journal publishes majorly in the area(s): Antibacterial agent & Docking (molecular). It has an ISSN identifier of 0009-4374. Over the lifetime, 13535 publication(s) have been published receiving 378733 citation(s). more


Journal ArticleDOI: 10.1016/J.EJMECH.2015.04.040
Abstract: This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded. more

Topics: Oxidative stress (63%), Free-radical theory of aging (62%), Antioxidant (55%) more

1,173 Citations

Journal ArticleDOI: 10.1016/S0223-5234(00)01189-2
C. Oliver Kappe1Institutions (1)
Abstract: In 1893, the synthesis of functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea and ethyl acetoacetate was reported for the first time by P. Biginelli. In the past decades, such Biginelli-type dihydropyrimidones have received a considerable amount of attention due to the interesting pharmacological properties associated with this heterocyclic scaffold. In this review, we highlight recent developments in this area, with a focus on the DHPMs recently developed as calcium channel modulators, alpha(1a) adrenoceptor-selective antagonists and compounds that target the mitotic machinery. more

Topics: Biginelli reaction (63%), Literature survey (53%)

1,114 Citations

Journal ArticleDOI: 10.1016/J.EJMECH.2006.09.019
Zdzisława Nowakowska1Institutions (1)
Abstract: Chalcones, considered as the precursors of flavonoids and isoflavonoids, are abundant in edible plants, and have also been shown to display a diverse array of pharmacological activities. The purpose of this review is to provide an overview of the pharmacological activity of synthetic and naturally occurring chalcones. This review is complementary to earlier reviews and covers more recent reports of antimicrobial activity of chalcones (antibacterial and antifungal), as well as antileishmanial, antimalarial, antiviral and anti-inflammatory activities of these compounds. more

Topics: Antibacterial agent (52%)

856 Citations

Journal ArticleDOI: 10.1016/S0223-5234(03)00012-6
Li Li Di1, Edward H. Kerns1, Kristi Fan1, Oliver McConnell1  +1 moreInstitutions (1)
Abstract: The recent advances in high throughput screening for biological activities and combinatorial chemistry have greatly expanded the number of drug candidates. Rapid screening for BBB penetration potential early in drug discovery programs provides important information for compound selection and guidance of synthesis for desirable CNS properties. In this paper, we discuss a modification of the parallel artificial membrane permeation assay (PAMPA) for the prediction of blood-brain barrier penetration (PAMPA-BBB). The assay was developed with 30 structurally diverse commercial drugs and validated with 14 Wyeth Research compounds. The PAMPA-BBB assay has the advantages of: predicting passive blood-brain barrier penetration with high success, high throughput, low cost, and reproducibility. more

787 Citations

Journal ArticleDOI: 10.1016/J.EJMECH.2004.10.001
Claude Monneret1Institutions (1)
Abstract: Histones are small basic proteins that, by complexing wtih DNA, form the nucleosome core. Repetitive units of this nucleosome led to the chromatin in which all the human genome is packaged. Histones can be in one of the two antagonist forms, acetylated or deacetylated, equilibrium regulated by the corresponding enzymes, histone acetylases and histones deacetylases (HDACs). Inhibition of HDACs represents a new strategy in human cancer therapy since these enzymes play a fundamental role in regulating gene expression and chromatin assembly. They are potent inducers of growth arrest, differentiation and apoptosis of tumor cells. A wide variety of HDACs of both natural and synthetic origin has been reported. Except depsispeptide FK228, natural HDACs (trichostatin (TSA), depudecin, trapoxins, apicidins) as well as sodium butyrate, phenylbutyrate and suberoyl anilide hydroxamic acid (SAHA), while effective in vivo, are inefficient due to instability and low retention. Subsequently, synthetic analogs isolated from screening libraries (oxamflatin, scriptaid) were discovered as havind a common structure with TSA and SAHA: an hydroxamic acid zinc-binding group linked via a spacer (5 or 6 CH2) to a hydrophobic group. Design of a second generation of HDACs was based upon these data affording potent HDACs such as LAQ824 and PDX101 currently under phase I clinical trials. Simultaneously, synthetic benzamide-containing HDACs were reported and two of them, MS-275 and CI-994, have reached phase II and I clinical trials, respectively. more

Topics: Histone deacetylase (56%), Phenylbutyrate (56%), Histone (55%) more

786 Citations

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Journal's top 5 most impactful authors

Claudiu T. Supuran

99 papers, 2.8K citations

Hong-Min Liu

44 papers, 1.3K citations

Erik De Clercq

43 papers, 1.6K citations

Jan Balzarini

41 papers, 1.4K citations

Ettore Novellino

37 papers, 587 citations

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