1,721,229 research outputs found
Sintesi e attività inibitoria selettiva sull’isoforma B delle MAO di derivati alchiliden-(4-ariltiazol-2-il)idrazonici
No full textNon-classical and selective carbonic anhydrase inhibitors: new scaffolds in the limelight?
No full textSelective carbonic anhydrase IX inhibitors based on coumarin scaffold as promising antimetastatic agents: WO2012070024
No full textSynthesis and biological evaluation of a new thiazole derivative, inducing histone hypoacetylation and apoptosis in human leukemia cells
No full textEnzyme-mediated activation of prodrugs
No full textThe development of potent drugs is always a challenging task and is often complicated by the number of pharmacokinetic and formulation limitations they suffer from. In addition, selectivity issues and targeting purposes make the regulatory approval a difficult-to-gain achievement. In this context, prodrugs strategy is widely employed and successful, especially, when a rational design is performed. Thus prodrugs are generated by introducing specific moieties or masking of already present chemical groups in the drug compounds in order to make them inactive or less active and allow a selective in vivo conversion into the corresponding active metabolites. The bioactivation process is mediated by chemical reactions due to the tissue microenvironment of the absorption or active site, e.g., the pH—acidic in the stomach or basic in the intestines—or reductive—in hypoxic cancers—or by the mediation of specific enzymes or classes of enzymes. Herein, we present an overview of enzymes involved in prodrugs activation, discussed according to the international enzyme classification (EC). Also, representative examples from the clinics are reported
New Frontiers in Selective Human MAO-B Inhibitors
Full text linkAccumulating evidence shows a relationship between the human MAO-B (hMAO-B) enzyme and neuropsychiatric/degenerative disorder, personality traits, type II alcoholism, borderline personality disorders, aggressiveness and violence in crime, obsessive-compulsive disorder, depression, suicide, schizophrenia, anorexia nervosa, migraine, dementia, and PD. Thus, MAO-B represents an attractive target for the treatment of a number of human diseases. The discovery, development, and therapeutic use of drugs that inhibit MAO-B are major challenges for future therapy. Various compounds and drugs that selectively target this isoform have been discovered recently. These agents are synthetic compounds or natural products and their analogues, including chalcones, pyrazoles, chromones, coumarins, xanthines, isatin derivatives, thiazolidin-diones, (thiazol-2-yl)hydrazones, and analogues of marketed drugs. Despite considerable efforts in understanding the binding interaction with specific substrates or inhibitors, structural information available for the rational design of new hMAO-B inhibitors remains unsatisfactory. Therefore, the quest for novel, potent, and selective hMAO-B inhibitors remains of high interest
Nature as a source and inspiration for human monoamine oxidase B (hMAO-B) inhibition: A review of the recent advances in chemical modification of natural compounds
No full textIntroduction: Over the past 5 years, we have witnessed intense research activity about the biological potential of natural products (NPs) as human monoamine oxidase B (hMAO-B) inhibitors. Despite the promising inhibitory activity, natural compounds often suffer from pharmacokinetic lissues, such as poor aqueous solubility, extensive metabolism, and low bioavailability. Areas covered: This review provides an overview of the current landscape NPs as selective hMAO-B inhibitors and highlights their use as a starting scaffold to design (semi)synthetic derivatives to overcome the therapeutic (pharmacodynamic and pharmacokinetic) limitations of NPs and to obtain more robust structure-activity relationships (SARs) for each scaffold. Expert opinion: All the natural scaffolds herein presented displayed a broad chemical diversity. The knowledge of their biological activity as inhibitors of hMAO-B enzyme allows the positive correlations associated with the consumption of specific food or the possible herb-drug interactions and suggests to the Medicinal Chemists how to address chemical functionalization to obtain more potent and selective compounds
Mechanisms of action of carbonic anhydrase inhibitors: compounds that bind “out of the binding site” and compounds with an unknown mechanism of action
No full textSo far, the design of human carbonic anhydrase (CA) inhibitors has been easily driven by the introduction of specific Zinc Binding Groups (ZBGs) (primary and secondary sulfonamides and their bioisosteres, dithiocarbamates, phosphonates, hydroxamic acids, and so on), which directly or indirectly block the enzyme-mediated catalytic CO2 hydration. All these inhibitors have been elegantly characterized by X-ray diffraction studies of hCA II-inhibitor adducts. The results led to the discovery of several drug candidates potent and selective for clinical purposes. Conversely, the most exciting innovation was the proposal of an alternative mechanism of inhibition targeting the proton shuttle His64 out of the binding site. Moreover, new chemotypes without the above described moieties are emerging as endowed with an unknown mechanism of interaction. New scenarios could be observed within these scaffold to finely modulate CA activity
Effects of processing on the organoleptic and nutritional properties of blueberry–derived products
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