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Organic & Biomolecular Chemistry Oct 2014This review provides insight into the variety of structures and biological activities found in the non-isoprenoid family of polyene natural products and examines the... (Review)
Review
This review provides insight into the variety of structures and biological activities found in the non-isoprenoid family of polyene natural products and examines the strategies and synthetic methods applied for the polyenic components in particular by way of examples.
Topics: Biological Products; Molecular Structure; Polyenes
PubMed: 25188767
DOI: 10.1039/c4ob01337a -
Revista Espanola de Quimioterapia :... Nov 2023New antifungal agents are needed to overcome limitations of available ones such as poor pharmacokinetic traits, toxicity, drug-drug interactions, limited clinical... (Review)
Review
New antifungal agents are needed to overcome limitations of available ones such as poor pharmacokinetic traits, toxicity, drug-drug interactions, limited clinical efficacy, and emerging antifungal resistance. New antifungal drugs belong to well-known families (azoles, polyenes, or beta-d-glucan synthase inhibitors) or to drug families showing completely new mechanisms of action. Some drugs have a head start in terms of potential to reach the clinical setting and are here reviewed.
Topics: Humans; Antifungal Agents; Mycoses; Azoles; Drug Resistance, Fungal; Polyenes
PubMed: 37997874
DOI: 10.37201/req/s01.14.2023 -
Microbial Drug Resistance (Larchmont,... Oct 2021is the second frequent etiologic agent of mucosal and invasive candidiasis. Based on the recent developments in molecular methods, has been introduced as a complex... (Review)
Review
is the second frequent etiologic agent of mucosal and invasive candidiasis. Based on the recent developments in molecular methods, has been introduced as a complex composed of , , and . The four main classes of antifungal drugs effective against are pyrimidine analogs (flucytosine), azoles, echinocandins, and polyenes. Although the use of antifungal drugs is related to the predictable development of drug resistance, it is not clear why is able to rapidly resist against multiple antifungals in clinics. The enhanced incidence and antifungal resistance of and the high mortality and morbidity need more investigation regarding the resistance mechanisms and virulence associated with ; additional progress concerning the drug resistance of has to be further prevented. The present review highlights the mechanism of resistance to antifungal drugs in .
Topics: Antifungal Agents; Azoles; Candida glabrata; Drug Resistance, Fungal; Echinocandins; Global Health; Polyenes; Pyrimidines
PubMed: 33956513
DOI: 10.1089/mdr.2020.0235 -
The Journal of Organic Chemistry Jun 2023A highly regiospecific vinylogous carbene insertion protocol for direct asymmetric C-H functionalization of indoles with arylvinyldiazoacetates has been developed. Under...
A highly regiospecific vinylogous carbene insertion protocol for direct asymmetric C-H functionalization of indoles with arylvinyldiazoacetates has been developed. Under the catalysis of simple Rh(I)/chiral diene complexes, the reaction occurs solely at the vinylogous position of the vinylcarbenoid with exceptional selectivity and enantiocontrol. It provides an efficient way to obtain an interesting class of chiral indole scaffolds bearing an α,β-unsaturated ester unit and a -diaryl carbon stereocenter in good yields (≤99%) with excellent enantioselectivities (≤96%) at room temperature.
Topics: Rhodium; Stereoisomerism; Catalysis; Indoles; Polyenes
PubMed: 36724384
DOI: 10.1021/acs.joc.2c02624 -
Applied and Environmental Microbiology May 2021Biofilms are the predominant bacterial lifestyle and can protect microorganisms from environmental stresses. Multispecies biofilms can affect the survival of enteric...
Biofilms are the predominant bacterial lifestyle and can protect microorganisms from environmental stresses. Multispecies biofilms can affect the survival of enteric pathogens that contaminate food products, and thus, investigating the underlying mechanisms of multispecies biofilms is essential for food safety and human health. In this study, we investigated the ability of the natural isolate Bacillus subtilis PS-216 to restrain Campylobacter jejuni biofilm formation and adhesion to abiotic surfaces as well as to disrupt preestablished C. jejuni biofilms. Using confocal laser scanning microscopy and colony counts, we demonstrate that the presence of B. subtilis PS-216 prevents C. jejuni biofilm formation, decreases growth of the pathogen by 4.2 log, and disperses 26-h-old preestablished C. jejuni biofilms. Furthermore, the coinoculation of B. subtilis and C. jejuni interferes with the adhesion of C. jejuni to abiotic surfaces, reducing it by 2.4 log. We also show that contact-independent mechanisms contribute to the inhibitory effect of B. subtilis PS-216 on C. jejuni biofilm. Using B. subtilis mutants in genes coding for nonribosomal peptides and polyketides revealed that bacillaene significantly contributes to the inhibitory effect of B. subtilis PS-216. In summary, we show a strong potential for the use of B. subtilis PS-216 against C. jejuni biofilm formation and adhesion to abiotic surfaces. Our research could bring forward novel applications of B. subtilis in animal production and thus contribute to food safety. Campylobacter jejuni is an intestinal commensal in animals (including broiler chickens) but also the most frequent cause of bacterial foodborne infection in humans. This pathogen forms biofilms which enhance survival of C. jejuni in food processing and thus threaten human health. Probiotic bacteria represent a potential alternative in the prevention and control of foodborne infections. The beneficial bacterium Bacillus subtilis has an excellent probiotic potential to reduce C. jejuni in the animal gastrointestinal tract. However, data on the effect of B. subtilis on C. jejuni biofilms are scarce. Our study shows that the B. subtilis natural isolate PS-216 prevents adhesion to the abiotic surfaces and the development of submerged C. jejuni biofilm during coculture and destroys the preestablished C. jejuni biofilm. These insights are important for development of novel applications of B. subtilis that will reduce the use of antibiotics in human and animal health and increase productivity in animal breeding.
Topics: Bacillus subtilis; Bacterial Adhesion; Biofilms; Biological Control Agents; Campylobacter jejuni; Mutation; Polyenes; Polystyrenes
PubMed: 33837012
DOI: 10.1128/AEM.02955-20 -
Chemistry (Weinheim An Der Bergstrasse,... Aug 2021Polyene cyclizations generate molecular complexity from a linear polyene in a single step. While methods to initiate these cyclizations have been continuously expanded...
Polyene cyclizations generate molecular complexity from a linear polyene in a single step. While methods to initiate these cyclizations have been continuously expanded and improved over the years, the majority of polyene substrates are still limited to simple alkyl-substituted alkenes. In this study, we took advantage of the unique reactivity of higher-functionalized bifunctional alkenes. The realization of a polyene tetracyclization of a dual nucleophilic aryl enol ether involving a transannular endo-termination step enabled the total synthesis of the tricyclic diterpenoid pimara-15-en-3α-8α-diol. The highly flexible and modular route allowed for the preparation of a diverse library of cyclization precursors specifically designed for the total synthesis of the tetracyclic nor-diterpenoid norflickinflimiod C. The tetracyclization of three diversely substituted allenes enabled access to complex pentacyclic products and provided a detailed insight into the underlying reaction pathways.
Topics: Abietanes; Biological Products; Cyclization; Polyenes; Stereoisomerism
PubMed: 34213030
DOI: 10.1002/chem.202101926 -
Bulletin of Experimental Biology and... Aug 2023We studied the effect of amphotericin B (2.5×10 and 5.4×10 M) on osmotic resistance and surface cytoarchitectonics of donor blood erythrocytes. Antibiotic at a...
We studied the effect of amphotericin B (2.5×10 and 5.4×10 M) on osmotic resistance and surface cytoarchitectonics of donor blood erythrocytes. Antibiotic at a concentration of 2.5×10 M induced most pronounced changes in the studied parameters, which can be related to the specifics of the spatial organization of the cholesterol-amphotericin B complexes at different stoichiometric ratios of the components and their ability to pore formation in the membranes. Cholesterol binding to the polyene antibiotic and the appearance of perforations in the plasma membrane lead to accumulation of reversibly and irreversibly deformed cells and their hemolysis. The appearance of a large number of irreversibly deformed erythrocytes indicates an impaired ability to elastic deformation in the microcirculatory stream, which can lead to disruption of their functions in vivo and intravascular hemolysis.
Topics: Humans; Amphotericin B; Anti-Bacterial Agents; Microcirculation; Polyenes; Erythrocytes; Cholesterol; Hemolysis
PubMed: 37770787
DOI: 10.1007/s10517-023-05888-x -
Current Topics in Medicinal Chemistry 2018Cryptococcosis is one of the major invasive fungal infections distributed worldwide with high mortality rate. C. neoformans and C. gattii are the major organisms that... (Review)
Review
Cryptococcosis is one of the major invasive fungal infections distributed worldwide with high mortality rate. C. neoformans and C. gattii are the major organisms that cause various types of infections. Anti-fungal resistances exhibited by the mentioned species of Cryptococcus threaten their effective prevention and treatment. There is limited information available on human to human transmission of the pathogen and virulent factors that are responsible for Cryptococcus mediated infections. Hence, there is high scope for understanding the mechanism, probable drug targets and scope of developing natural therapeutic agents that possess high relevance to pharmaceutical biotechnology and medicinal chemistry. The proposed review illustrates the role of computer-aided virtual screening for the screening of probable drug targets and identification of natural lead candidates as therapeutic remedies. The review initially focuses on the current perspectives on cryptococcosis, major metabolic pathways responsible for the pathogenesis, conventional therapies and associated drug resistance, challenges and scope of structure-based drug discovery. The review further illustrates various approaches for the prediction of unknown drug targets, molecular modeling works, screening of natural compounds by computational virtual screening with ideal drug likeliness and pharmacokinetic features, application of molecular docking studies and simulation. Thus, the present review probably provides AN insight into the role of medicinal chemistry and computational drug discovery to combat Cryptococcus infections and thereby open a new paradigm for the development of novel natural therapeutic against various drug targets for cryptococcal infections.
Topics: Animals; Antifungal Agents; Azoles; Biological Products; Computer-Aided Design; Cryptococcosis; Cryptococcus gattii; Cryptococcus neoformans; Drug Design; Drug Evaluation, Preclinical; Echinocandins; Humans; Models, Molecular; Polyenes
PubMed: 30659541
DOI: 10.2174/1568026619666190119145434 -
Scientific Reports May 2017Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from...
Bioactive natural products from mangrove-derived actinomycetes are important sources for discovery of drug lead compounds. In this study, an extract prepared from culture of an actinomycete Streptomyces sp. ZQ4BG isolated from mangrove soils was found to have activity in inhibiting proliferation of glioma cells. Large culture of this mangrove actinomycete in Gause's liquid medium resulted in isolation of seven novel polyene-polyol macrolides, named as flavofungins III-IX (3-9), together with known flavofungins I (1) and II (2) and spectinabilin (10). Structures of these isolated compounds were elucidated by extensive NMR analyses and HRESIMS data. The stereochemical assignments were achieved by a combination of NOE information, universal NMR database, and chemical reactions including preparation of acetonide derivatives and Mosher esters. Flavofungins IV-VIII (4-8) are rare 32-membered polyene-polyol macrolides with a tetrahydrofuran ring, while flavofungin IX (9) represents the first example of this type of macrolide with a unique oxepane ring. Flavofungins I (1) and II (2) and spectinabilin (10) showed anti-glioma and antifungal activities.
Topics: Carbon-13 Magnetic Resonance Spectroscopy; Macrolides; Polyenes; Polymers; Proton Magnetic Resonance Spectroscopy; Rhizophoraceae; Streptomyces
PubMed: 28490799
DOI: 10.1038/s41598-017-01912-z -
Biochemistry Oct 2021A transmembrane proton gradient is generated and maintained by proton pumps in a cell. Metagenomics studies have recently identified a new category of rhodopsin...
A transmembrane proton gradient is generated and maintained by proton pumps in a cell. Metagenomics studies have recently identified a new category of rhodopsin intermediates between type-1 rhodopsins and heliorhodopsins, named schizorhodopsins (SzRs). SzRs are light-driven inward proton pumps. Comprehensive resonance Raman measurements were conducted to characterize the structure of the retinal chromophore in the unphotolyzed state of four SzRs. The spectra of all four SzRs show that the retinal chromophore is in the all- and 15- configuration and that the Schiff base is protonated. The polyene chain is planar in the center of the retinal chromophore and is twisted in the vicinity of the protonated Schiff base. The protonated Schiff base in the SzRs forms a stronger hydrogen bond than that in outward proton-pumping rhodopsins. We determined that the hydrogen-bonding partner of the protonated Schiff base is not a water molecule but an amino acid residue, presumably an Asp residue in helix G. The present observations provide valuable insights into the inward proton-pumping mechanism of SzRs.
Topics: Archaea; Archaeal Proteins; Hydrogen Bonding; Polyenes; Proton Pumps; Rhodopsins, Microbial; Schiff Bases
PubMed: 34601881
DOI: 10.1021/acs.biochem.1c00529