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ACS Infectious Diseases Jan 2023Natamycin is a macrolide polyene antibiotic, characterized by a potent broad spectrum antifungal activity and low toxicity. However, it is not used for the treatment of...
Natamycin is a macrolide polyene antibiotic, characterized by a potent broad spectrum antifungal activity and low toxicity. However, it is not used for the treatment of systemic mycoses due to its low bioavailability and low solubility in aqueous solutions. In order to create new semisynthetic antifungal agents for treatment of mycoses, a series of water-soluble amides of natamycin were synthesized. Antifungal activities of natamycin derivatives were investigated against , including a panel of clinical isolates and filamentous fungi. Toxicity for mammalian cells was assayed by monitoring antiproliferative activity against human postnatal fibroblasts (HPF) and human embryonic kidney cells (HEK293). By comparing leakage of contents from ergosterol versus cholesterol containing vesicles, a ratio that characterizes the efficacy and safety of natamycin and its derivatives was determined (EI, efficiency index). Ability of all tested semisynthetic natamycines to prevent proliferation of the yeast cells was comparable or even slightly higher to those of parent antibiotic. Interestingly, amide was more potent than natamycin () against all tested strains (MIC values 2 μg/mL vs 8 μg/mL, respectively). Among 7 derivatives, amide with long lipophilic side chains showed the highest and strong antifungal activity in vitro but was more toxic against HPF. In vivo experiments with amide showed in vivo efficacy on a mouse candidemia model with a larger LD/ED ratio in comparison to amphotericin B.
Topics: Animals; Mice; Humans; Natamycin; Antifungal Agents; Anti-Bacterial Agents; HEK293 Cells; Polyenes; Mycoses; Candida; Saccharomyces cerevisiae; Mammals
PubMed: 36563312
DOI: 10.1021/acsinfecdis.2c00237 -
Molecules (Basel, Switzerland) Aug 2021This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound...
This paper presents the results of the first part of testing a novel electrospun fiber mat based on a unique macromolecule: polyisobutylene (PIB). A PIB-based compound containing zinc oxide (ZnO) was electrospun into self-supporting mats of 203.75 and 295.5 g/m that were investigated using a variety of techniques. The results show that the hydrophobic mats are not cytotoxic, resist fibroblast cell adhesion and biofilm formation and are comfortable and easy to breathe through for use as a mask. The mats show great promise for personal protective equipment and other applications.
Topics: Biofilms; Cell Adhesion; Cells, Cultured; Fibroblasts; Humans; Materials Testing; Nanofibers; Polyenes; Polymers; Zinc Oxide
PubMed: 34500639
DOI: 10.3390/molecules26175207 -
Organic Letters Apr 2022The first total synthesis of the abietaquinone methide diterpenoid (-)-3-oxoisotaxodione is reported. The key enabling step is the use of a chiral bicyclic hydrazide as...
The first total synthesis of the abietaquinone methide diterpenoid (-)-3-oxoisotaxodione is reported. The key enabling step is the use of a chiral bicyclic hydrazide as an organocatalyst for the enantioselective polyene cyclization of a ()-polyene substrate to form the -decalin core of the natural product. The α-oxo--quinone methide unit is formed by a two-step oxidation from a phenol, enabling an efficient synthesis of the natural product.
Topics: Biological Products; Cyclization; Diterpenes; Oxidation-Reduction; Polyenes
PubMed: 35311261
DOI: 10.1021/acs.orglett.2c00444 -
Sub-cellular Biochemistry 2016Carotenoids are polyenes synthesized in plants and certain microorganisms and are pigments used by plants and animals in various physiological processes. Some of the... (Review)
Review
Carotenoids are polyenes synthesized in plants and certain microorganisms and are pigments used by plants and animals in various physiological processes. Some of the over 600 known carotenoids are capable of metabolic conversion to the essential nutrient vitamin A (retinol) in higher animals. Vitamin A also gives rise to a number of other metabolites which, along with their analogs, are known as retinoids. To facilitate discussion about these important molecules, a nomenclature is required to identify specific substances. The generally accepted rules for naming these important molecules have been agreed to by various Commissions of the International Union of Pure and Applied Chemistry and International Union of Biochemistry. These naming conventions are explained along with comparisons to more systematic naming rules that apply for these organic chemicals. Identification of the carotenoids and retinoids has been advanced by their chemical syntheses, and here, both classical and modern methods for synthesis of these molecules, as well as their analogs, are described. Because of their importance in biological systems, sensitive methods for the detection and quantification of these compounds from various sources have been essential. Early analyses that relied on liquid adsorption and partition chromatography have given way to high-performance liquid chromatography (HPLC) coupled with various detection methods. The development of HPLC coupled to mass spectrometry, particularly LC/MS-MS with Multiple Reaction Monitoring, has resulted in the greatest sensitivity and specificity in these analyses.
Topics: Animals; Carotenoids; Chromatography; Forecasting; Humans; Molecular Structure; Plants; Retinoids; Terminology as Topic; Vitamin A
PubMed: 27830499
DOI: 10.1007/978-94-024-0945-1_1 -
Journal of the Science of Food and... Oct 2022α-Carotene, one of the C carotenes, is a natural lipid-soluble terpene. The chemical structure of α-carotene is based on the unsaturated polyene chain skeleton, with... (Review)
Review
α-Carotene, one of the C carotenes, is a natural lipid-soluble terpene. The chemical structure of α-carotene is based on the unsaturated polyene chain skeleton, with an ε-ring and a β-ring on each side of the skeleton. α-Carotene is widely found in dietary fruits and vegetables, and the concentration depends on the plant species. In addition, processing methods and storage conditions used in the food and medical industries can alter the concentration of α-carotene in raw materials. This review of α-carotene summarizes the major studies on chemical structure, source, extraction, detection, biosynthesis, processing effect, bioactivity, medicine, and biotechnology. Whether α-carotene supplementation or a diet rich in fruits and vegetables has a positive effect on the prevention of cancer, cardiovascular disease, and other diseases is the focus of this study. © 2022 Society of Chemical Industry.
Topics: Biomedical Research; Carotenoids; Lutein; Vegetables
PubMed: 35478460
DOI: 10.1002/jsfa.11966 -
Organic Letters Aug 2015The first total synthesis of amphirionin-4 has been achieved using a combination of cross-coupling strategies to access the polyene side chain and a chlorohydrin-based...
The first total synthesis of amphirionin-4 has been achieved using a combination of cross-coupling strategies to access the polyene side chain and a chlorohydrin-based approach to construct the tetrahydrofuranol core. The remote C9-stereocenter was introduced through a Nozaki-Hiyama-Kishi coupling that proceeded with remote stereoinduction.
Topics: Biological Products; Dinoflagellida; Marine Biology; Molecular Structure; Polyenes; Polyketides
PubMed: 26172382
DOI: 10.1021/acs.orglett.5b01844 -
Macromolecular Rapid Communications Dec 2022The unprecedented growth and socioeconomic impacts of polyolefins clearly outline a major success story in the world of polymer science. Polyolefins...
The unprecedented growth and socioeconomic impacts of polyolefins clearly outline a major success story in the world of polymer science. Polyolefins revolutionizes industries such as health care, construction, and food packaging. Despite the benefits of polyolefins, there is a rising concern for the environment due to high production volume (i.e., fossil fuel consumption), often short usage time, and problems related to waste management and accumulation in the natural environment. Creating a circular economy for polyolefins through effective recycling technologies has the potential to decrease the environmental impact of these materials. This perspective discusses polyolefins and their impact, existing and emerging recycling/upcycling solutions, and recycle-by-design alternatives that are challenging the status quo.
Topics: Polyenes; Plastics; Product Packaging; Polymers
PubMed: 35908163
DOI: 10.1002/marc.202200492 -
Applied Microbiology and Biotechnology May 2016The polyene macrolide group includes important antifungal drugs, to which resistance does not arise readily. Chemical and biological methods have been used in attempts... (Review)
Review
The polyene macrolide group includes important antifungal drugs, to which resistance does not arise readily. Chemical and biological methods have been used in attempts to make polyene antibiotics with fewer toxic side effects. Genome sequencing of producer organisms is contributing to this endeavour, by providing access to new compounds and by enabling yield improvement for polyene analogues obtained by engineered biosynthesis. This recent work is also enhancing bioinformatic methods for deducing the structures of cryptic natural products from their biosynthetic enzymes. The stereostructure of candicidin D has recently been determined by NMR spectroscopy. Genes for the corresponding polyketide synthase have been uncovered in several different genomes. Analysis of this new information strengthens the view that protein sequence motifs can be used to predict double bond geometry in many polyketides.Chemical studies have shown that improved polyenes can be obtained by modifying the mycosamine sugar that is common to most of these compounds. Glycoengineered analogues might be produced by biosynthetic methods, but polyene glycosyltransferases show little tolerance for donors other than GDP-α-D-mycosamine. Genome sequencing has revealed extending glycosyltransferases that add a second sugar to the mycosamine of some polyenes. NppY of Pseudonocardia autotrophica uses UDP-N-acetyl-α-D-glucosamine as donor whereas PegA from Actinoplanes caeruleus uses GDP-α-D-mannose. These two enzymes show 51 % sequence identity and are also closely related to mycosaminyltransferases. These findings will assist attempts to construct glycosyltransferases that transfer alternative UDP- or (d)TDP-linked sugars to polyene macrolactones.
Topics: Anti-Bacterial Agents; Biosynthetic Pathways; Glucosyltransferases; Macrolides; Polyenes; Streptomyces
PubMed: 27023916
DOI: 10.1007/s00253-016-7474-z -
Journal of the American Chemical Society Apr 2022A new polyene cyclization strategy exploiting β-ionyl derivatives was developed. Photoinduced deconjugation of the extended π-system within these chromophores unveils...
A new polyene cyclization strategy exploiting β-ionyl derivatives was developed. Photoinduced deconjugation of the extended π-system within these chromophores unveils a contrathermodynamic polyene that engages in a Heck bicyclization to afford [4.4.1]-propellanes. This cascade improves upon the limited regioselectivity achieved using existing biomimetic tactics and tolerates both electron-rich and electron-deficient (hetero)aryl groups. The utility of this approach was demonstrated with the diverted total synthesis of taxodione and salviasperanol, two isomeric abietane diterpenes that were previously inaccessible along the same synthetic pathway.
Topics: Abietanes; Cyclization; Polyenes; Stereoisomerism
PubMed: 35377634
DOI: 10.1021/jacs.2c02144 -
Methods in Molecular Biology (Clifton,... 2021Polyene antibiotics are macrolide antifungal compounds obtained by fermentation of producer Streptomyces strains. Here we describe commonly used methods for polyene...
Polyene antibiotics are macrolide antifungal compounds obtained by fermentation of producer Streptomyces strains. Here we describe commonly used methods for polyene production, detection, and their subsequent extraction and purification. While bioassays are used to detect these compounds based on their biological activity, quantification by spectrophotometry or high-performance liquid chromatography (HPLC ) relies on their physiochemical properties and is more reliable.
Topics: Anti-Bacterial Agents; Antifungal Agents; Biological Assay; Chromatography, High Pressure Liquid; Fermentation; Macrolides; Polyenes; Streptomyces
PubMed: 33977457
DOI: 10.1007/978-1-0716-1358-0_19