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Applied Microbiology and Biotechnology Jun 2021Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene...
Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene macrolides, pyranpolyenolides A (1) and B (2), and one new natural cyclic peptide (9), together with two known polyenes (7 and 8) and three known cyclic peptides (10-12), were isolated from a culture of the marine Streptomyces sp. MS110128. In addition, four new polyene macrolides, pyranpolyenolides C-F (3-6), were identified as olefin geometric isomers that were most likely produced by photochemical conversion during the cultivation or isolation procedures. The pyranpolyenolides are 32-membered macrolides endowed with a conjugated tetraene and several pairs of 1,3-dihydroxyl groups. Pyranpolyenolides that contain a hydropyran group have not been previously reported. Four cyclic peptides (9-12) showed significant activities against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant S. aureus with supporting MIC values ranging from 0.025 to 1.25 μg/mL. These cyclic peptides containing piperazic moieties showed moderate activities with MIC values of 12.5 μg/mL against Bacille Calmette Guerin (BCG), an attenuated form of the bovine. Additionally, cyclic peptide 12 showed moderate antifungal activity against Candida albicans with an MIC value of 12.5 μg/mL. KEY POINTS: • Discovery of new polyenes and cyclic peptides from a marine-derived Actinomycete. • Cyclic peptides containing piperazic moieties exhibited good antibacterial activity.
Topics: Animals; Anti-Bacterial Agents; Cattle; Macrolides; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Peptides, Cyclic; Polyenes; Polymers; Streptomyces
PubMed: 34146138
DOI: 10.1007/s00253-021-11226-w -
Current Opinion in Pharmacology Oct 2015The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are... (Review)
Review
The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are supported mainly by adult studies and extrapolation. Significant progress has been made to address this need in the last decade. Pre-clinical models and pharmacokinetic-pharmacodynamic (PK-PD) bridging studies supported by pediatric pharmacokinetic studies have investigated optimal dosing regimens for neonates and children. Here, we review the rationale for various antifungal regimens in infants and children.
Topics: Adult; Antifungal Agents; Child; Echinocandins; Humans; Pediatrics; Pharmacology, Clinical; Polyenes; Triazoles
PubMed: 26366938
DOI: 10.1016/j.coph.2015.08.009 -
The Journal of Organic Chemistry Aug 2022A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product β-parinaric acid and the total synthesis of...
A divergent formal synthesis of polyhydroxylated macrocyclic lactone (+)-aspicillin and polyene bioactive natural product β-parinaric acid and the total synthesis of non-terpenoid metabolite isolaurepan have been achieved using a ruthenium-catalyzed stereo- and chemoselective oxidative coupling reaction of easily accessible vinyl ketones and acrylates. The crucial transformation involves the efficient synthesis and functionalization of stereodefined ()-1,6-dioxo-2,4-dienes using simple reaction protocols, which enabled straightforward access to a diverse range of bioactive natural products.
Topics: Fatty Acids, Unsaturated; Oxepins; Polyenes; Ruthenium
PubMed: 35921130
DOI: 10.1021/acs.joc.2c01280 -
Organic & Biomolecular Chemistry Oct 2022A method for the mild and efficient synthesis of 1,3-dienylsulfonyl fluorides was developed dehalogenation of α-halo-1,3-dienylsulfonyl fluorides in the presence of...
A method for the mild and efficient synthesis of 1,3-dienylsulfonyl fluorides was developed dehalogenation of α-halo-1,3-dienylsulfonyl fluorides in the presence of zinc powder and acetic acid, achieving exclusive chemo- and stereoselectivities. This protocol was successfully applied to the synthesis of heterocyclic dienylsulfonyl fluorides and polyene sulfonyl fluoride.
Topics: Fluorides; Polyenes; Powders; Zinc
PubMed: 36168842
DOI: 10.1039/d2ob01434c -
Molecular Phylogenetics and Evolution Oct 2018Antibiotics are the most marvelous evolutionary products of microbes to obtain competitive advantage and maintain ecological balance. However, the origination and...
Antibiotics are the most marvelous evolutionary products of microbes to obtain competitive advantage and maintain ecological balance. However, the origination and development of antibiotics has yet to be explicitly investigated. Due to diverse structures and similar biosynthesis, glycosylated polyene macrolides (gPEMs) were chosen to explore antibiotic evolution. A total of 130 candidate and 38 transitional gPEM clusters were collected from actinomycetes genomes, providing abundant references for phenotypic gaps in gPEM evolution. The most conserved parts of gPEM biosynthesis were found and used for phylogeny construction. On this basis, we proposed ancestral gPEM clusters at different evolutionary stages and interpreted the possible evolutionary histories in detail. The results revealed that gPEMs evolved from small rings to large rings and continuously increased structural diversity through acquiring, discarding and exchanging genes from different evolutionary origins, as well as co-evolution of functionally related proteins. The combination of horizontal gene transfers, environmental effects and host preference resulted in the diversity and worldwide distribution of gPEMs. This study is not only a useful exploration on antibiotic evolution but also an inspiration for diversity and biogeographic investigations on antibiotics in the era of Big Data.
Topics: Anti-Bacterial Agents; Biosynthetic Pathways; Conserved Sequence; Evolution, Molecular; Genome; Glycosylation; Macrolides; Phylogeny; Polyenes; Proteins
PubMed: 29885934
DOI: 10.1016/j.ympev.2018.06.005 -
Organic Letters Mar 2021Although substituted benzimidazoles are common substructures in bioactive small molecules, synthetic methods for their derivatization are still limited. Previously,...
Although substituted benzimidazoles are common substructures in bioactive small molecules, synthetic methods for their derivatization are still limited. Previously, several enantioselective allylation reactions of benzimidazoles were reported that functionalize the nucleophilic nitrogen atom. Herein we describe a reversal of this inherent selectivity toward -allylation by using electrophilic -OPiv benzimidazoles with readily available 1,3-dienes as nucleophile precursors. This CuH-catalyzed approach utilizes mild reaction conditions, exhibits broad functional-group compatibility, and exclusively forms the C2-allylated product with excellent stereoselectivity.
Topics: Allyl Compounds; Benzimidazoles; Catalysis; Copper; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 33646778
DOI: 10.1021/acs.orglett.1c00306 -
Chemphyschem : a European Journal of... Feb 2021This review is centered on the linear conjugated polyenes, which encompasses chromatic biomolecules, such as carotenoids, polyunsaturated aldehydes and polyolefinic... (Review)
Review
This review is centered on the linear conjugated polyenes, which encompasses chromatic biomolecules, such as carotenoids, polyunsaturated aldehydes and polyolefinic fatty acids. The linear extension of the conjugated double bonds in these molecules is the main feature that determines the spectroscopic properties as light-absorbing. These classes of compounds are responsible for the yellow, orange, red and purple colors which are observed in their parent flora and fauna in nature. Raman spectroscopy has been used as analytical tool for the characterization of these molecules, mainly due to the strong light scattering produced by the delocalized pi electrons in the carbon chain. In addition, conjugated polyenes are one of the main target molecular species for astrobiology, and we also present a brief discussion of the use of Raman spectroscopy as one of the main analytical tools for the detection of polyenes extra-terrestrially.
Topics: Color; Polyenes; Spectrum Analysis, Raman
PubMed: 33225557
DOI: 10.1002/cphc.202000818 -
Journal of Infection and Chemotherapy :... Oct 2019Candida auris is a multidrug-resistant and emergent pathogen that has caused healthcare-associated infection outbreaks. Recently, C. auris has spread worldwide;... (Review)
Review
Candida auris is a multidrug-resistant and emergent pathogen that has caused healthcare-associated infection outbreaks. Recently, C. auris has spread worldwide; nevertheless, it was unexpectedly rare before 2009. Based on the molecular epidemiological analysis, C. auris may independently emerge at specific areas at first and recently may be transmitted to other continents. As C. auris cannot be detected using conventional methods, internally transcribed spacers, D1/D2 regions of the 26S rDNA sequencing, and/or matrix-assisted laser desorption ionization time-of-flight mass spectrometry method can be selected as comparatively accessible choices. Thus, detection of C. auris using the conventional method might be underestimated. In Japan, all C. auris strains were isolated from ear specimen and not from invasive mycoses. Japan strains were classified as an East Asian clade under a single clone. Although colonization, virulence, and infection pattern are almost the same as with other Candida species, its antifungal resistance is different. Fluconazole resistance is notably common, but resistance to all three classes of antifungals (azole, polyene, and echinocandin) rarely exists. Once C. auris is detected, screening, emphasis on hand hygiene adherence, use of single-patient room isolation, contact precaution, surveillance, and eradication from the environment and patients are appropriately required for infection control.
Topics: Antifungal Agents; Azoles; Candida; Candidiasis; Drug Resistance, Multiple, Fungal; Echinocandins; Fluconazole; Humans; Japan; Microbial Sensitivity Tests; Polyenes; Prevalence
PubMed: 31257156
DOI: 10.1016/j.jiac.2019.05.034 -
ACS Macro Letters Mar 2022A general and versatile synthetic strategy for producing practical quantities of a wide range of phenyl-group-terminated hetero- and homotelechelic semicrystalline...
A general and versatile synthetic strategy for producing practical quantities of a wide range of phenyl-group-terminated hetero- and homotelechelic semicrystalline polyethenes and amorphous atactic and semicrystalline isotactic poly(α-olefins) is reported. The phenyl groups serve as synthons for functionalities of additional classes of telechelic polyolefins that can be "unmasked" through simple high yielding postpolymerization reactions. A demonstration of the value of these materials as building blocks for structural classes of polyolefin-based synthetic polymers was provided by syntheses of well-defined polyolefin-polyester di- and triblock copolymers that were shown to adopt microphase-segregated nanostructured mesophases in the condensed phase.
Topics: Alkenes; Polyenes; Polyesters; Polymers
PubMed: 35575371
DOI: 10.1021/acsmacrolett.2c00108 -
Nutrition Research Reviews Dec 2023Many epidemiological studies have emphasised the relation between carotenoid dietary intake and their circulating concentrations and beneficial health effects, such as... (Review)
Review
Many epidemiological studies have emphasised the relation between carotenoid dietary intake and their circulating concentrations and beneficial health effects, such as lower risk of cardiometabolic diseases and cancer. However, there is dispute as to whether the attributed health benefits are due to native carotenoids or whether they are instead induced by their metabolites. Several categories of metabolites have been reported, most notably involving (a) modifications at the cyclohexenyl ring or the polyene chain, such as epoxides and geometric isomers, (b) excentric cleavage metabolites with alcohol-, aldehyde- or carboxylic acid-functional groups or (c) centric cleaved metabolites with additional hydroxyl, aldehyde or carboxyl functionalities, not counting their potential phase-II glucuronidated / sulphated derivatives. Of special interest are the apo-carotenoids, which originate in the intestine and other tissues from carotenoid cleavage by β-carotene oxygenases 1/2 in a symmetrical / non-symmetrical fashion. These are more water soluble and more electrophilic and, therefore, putative candidates for interactions with transcription factors such as NF-kB and Nrf2, as well as ligands for RAR-RXR nuclear receptor interactions. In this review, we discuss detected apo-carotenoids, their reported tissue concentrations, and potential associated health effects, focusing exclusively on the human situation and based on quantified / semi-quantified carotenoid metabolites proven to be present in humans.
Topics: Humans; Retinoids; Carotenoids; Neoplasms; Aldehydes
PubMed: 36380523
DOI: 10.1017/S095442242200021X