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Biochimica Et Biophysica Acta Aug 2014Polyene lipids and alkyne lipids allow study of lipid organization, dynamics and metabolism. Both types of lipids contain multiple bonds as the essential functional... (Review)
Review
Polyene lipids and alkyne lipids allow study of lipid organization, dynamics and metabolism. Both types of lipids contain multiple bonds as the essential functional group, leading to minimal disturbance of the hydrophobic properties on which the characteristic behavior of lipids is based. Polyene lipids can directly be traced due to their intrinsic fluorescence, while alkyne lipids need the copper-catalyzed click reaction to an azido-reporter for detection. This review describes recent developments in synthesis and application of both types of lipid analogs with emphasis on metabolic tracing and microscopy imaging. This article is part of a Special Issue entitled Tools to study lipid functions.
Topics: Alkynes; Hydrophobic and Hydrophilic Interactions; Lipids; Polyenes
PubMed: 24412758
DOI: 10.1016/j.bbalip.2013.12.018 -
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 -
Angewandte Chemie (International Ed. in... Jan 2023A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized...
A catalysis-based regioselective 1,4-fluorofunctionalization of trifluoromethyl substituted 1,3-dienes has been developed to access compact, highly functionalized products. The process allows E,Z-mixed dienes to be processed to a single E-alkene isomer, and leverages an inexpensive and operationally convenient I(I)/I(III) catalysis platform. The first example of catalytic 1,4-difluorination is disclosed and subsequently evolved to enable 1,4-hetero-difunctionalization, which allows δ-fluoro-alcohol and amine derivatives to be forged in a single operation. The protocol is compatible with a variety of nucleophiles including fluoride, nitriles, carboxylic acids, alcohols and even water thereby allowing highly functionalized products, with a stereocenter bearing both C(sp )-F and C(sp )-CF groups, to be generated rapidly. Scalability (up to 3 mmol), and facile post-reaction modifications are demonstrated to underscore the utility of the method in expanding organofluorine chemical space.
Topics: Polyenes; Isomerism; Alkenes; Catalysis; Alcohols
PubMed: 36345795
DOI: 10.1002/anie.202214906 -
International Journal of Molecular... Nov 2022are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may... (Review)
Review
are of great interest in the pharmaceutical industry as they produce a plethora of secondary metabolites that act as antibacterial and antifungal agents. They may thrive on their own in the soil, or associate with other organisms, such as plants or invertebrates. Some soil-derived strains exhibit hemolytic properties when cultivated on blood agar, raising the question of whether hemolysis could be a virulence factor of the bacteria. In this work we examined hemolytic compound production in 23 β-hemolytic isolates; of these 12 were soil-derived, 10 were arthropod-associated, and 1 was plant-associated. An additional human-associated sp. TR1341 served as a control. Mass spectrometry analysis suggested synthesis of polyene molecules responsible for the hemolysis: candicidins, filipins, strevertene A, tetrafungin, and tetrin A, as well as four novel polyene compounds (denoted here as polyene A, B, C, and D) in individual liquid cultures or paired co-cultures. The non-polyene antifungal compounds actiphenol and surugamide A were also identified. The findings indicate that the ability of to produce cytolytic compounds (here manifested by hemolysis on blood agar) is an intrinsic feature of the bacteria in the soil environment and could even serve as a virulence factor when colonizing available host organisms. Additionally, a literature review of polyenes and non-polyene hemolytic metabolites produced by is presented.
Topics: Humans; Streptomyces; Antifungal Agents; Anti-Bacterial Agents; Polyenes; Hemolysis; Virulence Factors
PubMed: 36499372
DOI: 10.3390/ijms232315045 -
Chemistry, An Asian Journal Dec 2022The reliance of both our life and industry on fossil resource and the alarming accumulation of polymeric materials in the environment have presented huge challenges to... (Review)
Review
The reliance of both our life and industry on fossil resource and the alarming accumulation of polymeric materials in the environment have presented huge challenges to sustainable society. Nowadays, utilization of renewable monomers as building blocks for polymeric materials has emerged as a hot topic and increasingly gained attention from chemists. As a class of biomass with abundance and low cost, terpenes are typical hydrocarbon-rich natural compounds, and some of them, such as myrcene and farnesene, are inherently suitable for coordination polymerization. In this review, we focus on the rare-earth metal catalyzed highly regio- and stereoselective polymerization of bio-based conjugated dienes, especially the ones from terpene-derived compounds with or without modifications. This review also discusses the future direction on the modification of these bio-based conjugated dienes.
Topics: Polymerization; Coordination Complexes; Metals, Rare Earth; Polyenes; Biomass; Polymers; Terpenes
PubMed: 36165273
DOI: 10.1002/asia.202200892 -
Fungal Genetics and Biology : FG & B Oct 2019Invasive aspergillosis caused by intrinsically resistant non-fumigatus Aspergillus species displays a poor outcome in immunocompromised patients. The polyene antifungal... (Review)
Review
Invasive aspergillosis caused by intrinsically resistant non-fumigatus Aspergillus species displays a poor outcome in immunocompromised patients. The polyene antifungal amphotericin B (AmB) remains to be "gold standard" in the treatment of invasive fungal infections. Aspergillus terreus is innately resistant to AmB, in vivo and in vitro. Till now, the exact mode of action in polyene resistance is not well understood. This review highlights the underlying molecular basis of AmB resistance in A. terreus, displaying data obtained from AmB susceptible A. terreus and AmB resistant A. terreus strains. The effect of AmB on main cellular and molecular functions such as fungal respiration and stress response pathways will be discussed in detail and resistance mechanisms will be highlighted. The fungal stress response machinery seems to be a major player in the onset of AmB resistance in A. terreus.
Topics: Amphotericin B; Animals; Antifungal Agents; Aspergillosis; Aspergillus; Cell Wall; Drug Resistance, Fungal; Ergosterol; Heat-Shock Proteins; Humans; Lipid Bilayers; Mice; Mitochondria; Oxidative Stress; Polyenes
PubMed: 31247322
DOI: 10.1016/j.fgb.2019.103247 -
The Journal of Organic Chemistry May 2022Ophiofuranones A and B, metabolites of the fungus , were synthesized in 16 steps and 12%/22% yield. The stereogenic centers were established by Sharpless...
Ophiofuranones A and B, metabolites of the fungus , were synthesized in 16 steps and 12%/22% yield. The stereogenic centers were established by Sharpless dihydroxylations and epoxidation, the 1,3-dienes via Wittig or HWE olefinations. The rings were closed through Knoevenagel-type condensation and lactonization. The ophiofuranones proved nontoxic at relevant concentrations against tumor cells, fibroblasts, and various bacteria and fungi. Ophiofuranone A and the monocyclic precursors were weakly active against microbial biofilms.
Topics: Polyenes
PubMed: 35471021
DOI: 10.1021/acs.joc.2c00521 -
Molecules (Basel, Switzerland) Aug 2020Boron and silicon-substituted 1,3-dienes and boron and silicon-substituted alkenes and alkynes have been known for years and the last 10 years have seen a number of new... (Review)
Review
Boron and silicon-substituted 1,3-dienes and boron and silicon-substituted alkenes and alkynes have been known for years and the last 10 years have seen a number of new reports of their preparation and use in Diels-Alder reactions. This review first covers boron-substituted dienes and dienophiles and then moves on to discuss silicon-substituted dienes and dienophiles.
Topics: Alkynes; Boron; Catalysis; Cycloaddition Reaction; Models, Molecular; Polyenes; Silicon; Stereoisomerism
PubMed: 32824327
DOI: 10.3390/molecules25163740 -
Drugs Sep 2017Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance,... (Review)
Review
Despite increasing rates of invasive fungal infections being reported globally, only a single antifungal drug has been approved during the last decade. Resistance, toxicity, drug interactions and restricted routes of administration remain unresolved issues. This review focuses on new antifungal compounds which are currently in various clinical phases of development. We discuss two azoles with a tetrazole moiety that allows selective activity against the fungal CYP: VT-1161 for Candida infections and VT-1129 for cryptococcal meningoencephalitis. We also discuss two glucan synthesis inhibitors: CD101, an echinocandin with an increased half-life, and SCY-078 with oral bioavailability and increased activity against echinocandin-resistant isolates. Among the polyenes, we discuss MAT023, an encochleated amphotericin B formulation that allows oral administration. Two novel classes of antifungal drugs are also described: glycosylphosphatidylinositol inhibitors, and the leading drug APX001, which disrupt the integrity of the fungal wall; and the orotomides, inhibitors of pyrimidine synthesis with the leading drug F901318. Finally, a chitin synthesis inhibitor and progress on human monoclonal antifungal antibodies are discussed.
Topics: Acetamides; Antibodies, Monoclonal; Antifungal Agents; Azoles; Chemistry, Pharmaceutical; Drug Development; Echinocandins; Humans; Mycoses; Piperazines; Polyenes; Pyrimidines; Pyrroles
PubMed: 28840541
DOI: 10.1007/s40265-017-0805-2