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Roczniki Panstwowego Zakladu Higieny 2023Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum...
Lutein and zeaxanthin are naturally occurring xanthophylls, mainly present in green, leafy vegetables and egg's yolk. Their presence is connected with blue spectrum light absorbance, including UV. This property, and fact, that these xanthophylls are accumulated by human eye's macula, leads to eye's protective functions of them including protection from age-related macular degeneration (AMD). Also, antioxidative features of lutein and zeaxanthin are boosting overall health of human body. Numerous studies proves anti-inflammatory and protective attributes of these compounds, based on many, different mechanisms. One of them is regulating redox potential in cells, and impact on expression of linked genes. In preventing of eye diseases, an important gene that is regulated by lutein and zeaxanthin is the Nrf2 gene, whose increased activity leads to optimizing the cellular response to reactive oxygen species (ROS) and preventing related diseases. Other research confirms antiproliferative properties of mentioned compounds in case of certain human cancer cell lines. There are e.g.: HepG2 (hepatitis cancer), MCF-7 (breast cancer), which treated in vitro with lutein solution showed reduction of cell growth. Lutein alone, during in vivo studies conducted on mice, exhibited also radioprotective properties, positively affecting the vitality of animals. Lutein provides also increasing of tolerance to UV radiation, reducing inflammatory processes in the skin and preventing oncogenesis. Low intake of lutein and zeaxanthin, associated with "western diet", rich in simple carbohydrates and processed food, common in developed countries, including Poland, is linked with diabetes and obesity incidence. Assuming, lutein and zeaxanthin significantly affect the well-being of the human body, and their appropriate amount in diet can help reduce risk of many diseases. For supplementation, the optimized dosage of these xanthophylls includes doses of 10 mg for lutein and 2 mg for zeaxanthin, and it is recommended to consume along with fats or meals rich in fats.
Topics: Humans; Animals; Mice; Lutein; Zeaxanthins; Xanthophylls; Macular Degeneration; Diet; Neoplasms
PubMed: 37577931
DOI: 10.32394/rpzh.2023.0266 -
Virulence Feb 2017Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare... (Review)
Review
Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare systems around the world. However, the clinically available armamentarium for invasive fungal diseases is limited to 3 main classes (i.e., polyenes, triazoles, and echinocandins), and each has defined limitations related to spectrum of activity, development of resistance, and toxicity. Further, current antifungal therapies are hampered by limited clinical efficacy, high rates of toxicity, and significant variability in pharmacokinetic properties. New antifungal agents, new formulations, and novel combination regimens may improve the care of patients in the future by providing improved strategies to combat challenges associated with currently available antifungal agents. Likewise, therapeutic drug monitoring may be helpful, but its present use remains controversial due to the lack of available data. This article discusses new facets of antifungal therapy with a focus on new antifungal formulations and the synergistic effects between drugs used in combination therapy.
Topics: Antifungal Agents; Drug Discovery; Drug Synergism; Drug Therapy, Combination; Echinocandins; Humans; Immunocompromised Host; Invasive Fungal Infections; Mycoses; Polyenes; Triazoles
PubMed: 27820668
DOI: 10.1080/21505594.2016.1257457 -
Molecules (Basel, Switzerland) Mar 2021In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of... (Review)
Review
In synthetic organic chemistry, there are very useful basic compounds known as building blocks. One of the main reactions wherein they are applied for the synthesis of complex molecules is the Diels-Alder cycloaddition. This reaction is between a diene and a dienophile. Among the most important dienes are the cyclic dienes, as they facilitate the reaction. This review considers the synthesis and reactivity of one of these dienes with special characteristics-it is cyclic and has an electron withdrawing group. This building block has been used for the synthesis of biologically active compounds and is present in natural compounds with interesting properties.
Topics: Cycloaddition Reaction; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 33809941
DOI: 10.3390/molecules26061772 -
Angewandte Chemie (International Ed. in... Mar 2020The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π...
The combination of electrocyclizations and cycloadditions accounts for the formation of a range of fascinating natural products. Cascades consisting of 8π electrocyclizations followed by a 6π electrocyclization and a cycloaddition are relatively common. We now report the synthesis of the tetramic acid PF-1018 through an 8π electrocyclization, the product of which is immediately intercepted by a Diels-Alder cycloaddition. The success of this pericyclic cascade was critically dependent on the substitution pattern of the starting polyene and could be rationalized through DFT calculations. The completion of the synthesis required the instalment of a trisubstituted double bond by radical deoxygenation. An unexpected side product formed through 4-exo-trig radical cyclization could be recycled through an unprecedented triflation/fragmentation.
Topics: Biological Products; Cyclization; Cycloaddition Reaction; Density Functional Theory; Electrochemical Techniques; Models, Molecular; Polyenes; Pyrrolidinones; Pyrrolizidine Alkaloids; Stereoisomerism
PubMed: 31788926
DOI: 10.1002/anie.201912452 -
Organic & Biomolecular Chemistry Jul 2015Cyanines are indispensable fluorophores that form the chemical basis of many fluorescence-based applications. A feature that distinguishes cyanines from other common... (Review)
Review
Cyanines are indispensable fluorophores that form the chemical basis of many fluorescence-based applications. A feature that distinguishes cyanines from other common fluorophores is an exposed polyene linker that is both crucial to absorption and emission and subject to covalent reactions that dramatically alter these optical properties. Over the past decade, reactions involving the cyanine polyene have been used as foundational elements for a range of biomedical techniques. These include the optical sensing of biological analytes, super-resolution imaging, and near-IR light-initiated uncaging. This review surveys the chemical reactivity of the cyanine polyene and the biomedical methods enabled by these reactions. The overarching goal is to highlight the multifaceted nature of cyanine chemistry and biology, as well as to point out the key role of reactivity-based insights in this promising area.
Topics: Biomedical Technology; Carbocyanines; Coloring Agents; Molecular Conformation; Polyenes
PubMed: 26052876
DOI: 10.1039/c5ob00788g -
Annual Review of Vision Science Oct 2016Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or... (Review)
Review
Recent progress in molecular understanding of the retinoid cycle in mammalian retina stems from painstaking biochemical reconstitution studies supported by natural or engineered animal models with known genetic lesions and studies of humans with specific genetic blinding diseases. Structural and membrane biology have been used to detect critical retinal enzymes and proteins and their substrates and ligands, placing them in a cellular context. These studies have been supplemented by analytical chemistry methods that have identified small molecules by their spectral characteristics, often in conjunction with the evaluation of models of animal retinal disease. It is from this background that rational therapeutic interventions to correct genetic defects or environmental insults are identified. Thus, most presently accepted modulators of the retinoid cycle already have demonstrated promising results in animal models of retinal degeneration. These encouraging signs indicate that some human blinding diseases can be alleviated by pharmacological interventions.
Topics: Animals; Disease Models, Animal; Humans; Retinal Diseases; Retinoids
PubMed: 27917399
DOI: 10.1146/annurev-vision-111815-114407 -
The Brazilian Journal of Infectious... 2017The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert... (Review)
Review
The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed.
Topics: Antifungal Agents; Area Under Curve; Aspergillosis; Azoles; Candidiasis; Dose-Response Relationship, Drug; Echinocandins; Humans; Latin America; Microbial Sensitivity Tests; Polyenes; Triazoles
PubMed: 27821250
DOI: 10.1016/j.bjid.2016.09.009 -
Journal of Ocular Pharmacology and... 2019Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis,... (Review)
Review
Polyenes and azoles constitute 2 major drug classes in the antifungal armamentarium used to treat fungal infections of the eye such as fungal keratitis, endophthalmitis, conjunctivitis, and blepharitis. These classes of drugs have come to occupy an important niche in ophthalmic antifungal therapy due to their broad spectrum of activity against a variety of filamentous and yeast-like fungi. Natamycin suspension (Natacyn), a polyene antifungal drug, is currently the only US FDA-approved formulation for treating ophthalmic fungal infections, whereas the other polyene and azole antifungals such as amphotericin B, fluconazole, itraconazole, ketoconazole, miconazole, voriconazole, and posaconazole are routinely used off-label in the clinical setting. Despite potent antifungal activity, the clinical utility of these agents in ophthalmic infections has been challenged by their physicochemical properties, the unique ocular anatomy and physiology, selective antifungal activity, ocular and systemic toxicity, emergence of resistance and cross-resistance, and absence of reliable techniques for developing a robust in vitro-in vivo correlation. This review discusses the aforementioned challenges and the common approaches undertaken to circumnavigate the difficulties associated with the polyene- and azole-based pharmacotherapy of ophthalmic fungal infections.
Topics: Animals; Antifungal Agents; Azoles; Eye Infections, Fungal; Humans; Microbial Sensitivity Tests; Ophthalmic Solutions; Polyenes
PubMed: 30481082
DOI: 10.1089/jop.2018.0089 -
Cold Spring Harbor Perspectives in... Nov 2014Successful treatment of infectious diseases requires choice of the most suitable antimicrobial agent, comprising consideration of drug pharmacokinetics (PK), including... (Review)
Review
Successful treatment of infectious diseases requires choice of the most suitable antimicrobial agent, comprising consideration of drug pharmacokinetics (PK), including penetration into infection site, pathogen susceptibility, optimal route of drug administration, drug dose, frequency of administration, duration of therapy, and drug toxicity. Antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) studies consider these variables and have been useful in drug development, optimizing dosing regimens, determining susceptibility breakpoints, and limiting toxicity of antifungal therapy. Here the concepts of antifungal PK/PD studies are reviewed, with emphasis on methodology and application. The initial sections of this review focus on principles and methodology. Then the pharmacodynamics of each major antifungal drug class (polyenes, flucytosine, azoles, and echinocandins) is discussed. Finally, the review discusses novel areas of pharmacodynamic investigation in the study and application of combination therapy.
Topics: Animals; Antifungal Agents; Disease Models, Animal; Echinocandins; Flucytosine; Humans; Mice; Mycoses; Polyenes; Rabbits; Rats; Triazoles
PubMed: 25384765
DOI: 10.1101/cshperspect.a019653 -
Marine Drugs May 2022Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene... (Review)
Review
Over the past few decades (covering 1972 to 2022), astounding progress has been made in the elucidation of structures, bioactivities and biosynthesis of polyene macrolactams (PMLs), but they have only been partially summarized. PMLs possess a wide range of biological activities, particularly distinctive fungal inhibitory abilities, which render them a promising drug candidate. Moreover, the unique biosynthetic pathways including β-amino acid initiation and pericyclic reactions were presented in PMLs, leading to more attention from inside and outside the natural products community. According to current summation, in this review, the chem- and bio-diversity of PMLs from marine and terrestrial sources are considerably rich. A systematic, critical and comprehensive overview is in great need. This review described the PMLs' general structural features, production strategies, biosynthetic pathways and the mechanisms of bioactivities. The challenges and opportunities for the research of PMLs are also discussed.
Topics: Biological Products; Biosynthetic Pathways; Polyenes
PubMed: 35736163
DOI: 10.3390/md20060360