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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 -
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 -
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 -
Clinical Pharmacokinetics May 2014Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of... (Review)
Review
Invasive fungal infections are a significant cause of morbidity and mortality in children. Successful management of these systemic infections requires identification of the causative pathogen, appropriate antifungal selection, and optimisation of its pharmacokinetic and pharmacodynamic properties to maximise its antifungal activity and minimise toxicity and the emergence of resistance. This review highlights salient scientific advancements in paediatric antifungal pharmacotherapies and focuses on pharmacokinetic and pharmacodynamic studies that underpin current clinical decision making. Four classes of drugs are widely used in the treatment of invasive fungal infections in children, including the polyenes, triazoles, pyrimidine analogues and echinocandins. Several lipidic formulations of the polyene amphotericin B have substantially reduced the toxicity associated with the traditional amphotericin B formulation. Monotherapy with the pyrimidine analogue flucytosine rapidly promotes the emergence of resistance and cannot be recommended. However, when used in combination with other antifungal agents, therapeutic drug monitoring of flucytosine has been shown to reduce high peak flucytosine concentrations, which are strongly associated with toxicity. The triazoles feature large inter-individual pharmacokinetic variability, although this pattern is less pronounced with fluconazole. In clinical trials, posaconazole was associated with fewer adverse effects than other members of the triazole family, though both posaconazole and itraconazole display erratic absorption that is influenced by gastric pH and the gastric emptying rate. Limited data suggest that the clinical response to therapy may be improved with higher plasma posaconazole and itraconazole concentrations. For voriconazole, pharmacokinetic studies among children have revealed that children require twice the recommended adult dose to achieve comparable blood concentrations. Voriconazole clearance is also affected by the cytochrome P450 (CYP) 2C19 genotype and hepatic impairment. Therapeutic drug monitoring is recommended as voriconazole pharmacokinetics are highly variable and small dose increases can result in marked changes in plasma concentrations. For the echinocandins, the primary source of pharmacokinetic variability stems from an age-dependent decrease in clearance with increasing age. Consequently, young children require larger doses per kilogram of body weight than older children and adults. Routine therapeutic drug monitoring for the echinocandins is not recommended. The effectiveness of many systemic antifungal agents has been correlated with pharmacodynamic targets in in vitro and in murine models of invasive candidiasis and aspergillosis. Further study is needed to translate these findings into optimal dosing regimens for children and to understand how these agents interact when multiple antifungal agents are used in combination.
Topics: Animals; Antifungal Agents; Child; Drug Interactions; Echinocandins; Humans; Polyenes; Pyrimidines; Triazoles
PubMed: 24595533
DOI: 10.1007/s40262-014-0139-0 -
Current Opinion in Investigational... Aug 2005SPK-843 is a water-soluble antibiotic under co-development by Aparts and Kaken for the potential treatment of systemic fungal infections. By November 2004, SPK-843 was... (Review)
Review
SPK-843 is a water-soluble antibiotic under co-development by Aparts and Kaken for the potential treatment of systemic fungal infections. By November 2004, SPK-843 was in phase II trials for systemic mycosis.
Topics: Animals; Antifungal Agents; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Mycoses; Patents as Topic; Polyenes; Structure-Activity Relationship
PubMed: 16121692
DOI: No ID Found -
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 -
International Journal of Molecular... May 2024One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the...
DFT and TD-DFT Investigations for the Limitations of Lengthening the Polyene Bridge between N,N-dimethylanilino Donor and Dicyanovinyl Acceptor Molecules as a D-π-A Dye-Sensitized Solar Cell.
One useful technique for increasing the efficiency of organic dye-sensitized solar cells (DSSCs) is to extend the π-conjugated bridges between the donor (D) and the acceptor (A) units. The present study used the DFT and TD-DFT techniques to investigate the effect of lengthening the polyene bridge between the donor N, N-dimethyl-anilino and the acceptor dicyanovinyl. The results of the calculated key properties were not all in line with expectations. Planar structure was associated with increasing the π-conjugation linker, implying efficient electron transfer from the donor to the acceptor. A smaller energy gap, greater oscillator strength values, and red-shifted electronic absorption were also observed when the number of polyene units was increased. However, some results indicated that the potential of the stated dyes to operate as effective dye-sensitized solar cells is limited when the polyene bridge is extended. Increasing the polyene units causes the HOMO level to rise until it exceeds the redox potential of the electrolyte, which delays regeneration and impedes the electron transport cycle from being completed. As the number of conjugated units increases, the terminal lobes of HOMO and LUMO continue to shrink, which affects the ease of intramolecular charge transfer within the dyes. Smaller polyene chain lengths yielded the most favorable results when evaluating the efficiency of electron injection and regeneration. This means that the charge transfer mechanism between the conduction band of the semiconductor and the electrolyte is not improved by extending the polyene bridge. The open circuit voltage (V) was reduced from 1.23 to 0.70 V. Similarly, the excited-state duration (τ) decreased from 1.71 to 1.23 ns as the number of polyene units increased from n = 1 to n = 10. These findings are incompatible with the power conversion efficiency requirements of DSSCs. Therefore, the elongation of the polyene bridge in such D-π-A configurations rules out its application in solar cell devices.
Topics: Solar Energy; Polyenes; Coloring Agents; Density Functional Theory; Aniline Compounds; Electron Transport
PubMed: 38891775
DOI: 10.3390/ijms25115586 -
Drug Design, Development and Therapy 2023Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year... (Review)
Review
Vulvovaginal candidiasis (VVC) is experienced by an estimated 75% of women at least once in their lifetime and is recurrent, defined as three or more infections per year (RVVC) in 5-9%. Candida albicans is the most common causative agent, but up to 19% of infections may be related to non-albicans species. Available treatment options for VVC have consisted of oral and topical azoles (except for topical nystatin, a polyene). Oral polyenes are not absorbed and therefore not effective for VVC. Fluconazole is the only oral medication FDA approved for VVC. None of these treatments are FDA approved for RVVC. Ibrexafungerp, a triterpenoid fungicidal agent, was FDA approved in 2021, becoming the first oral non-azole agent for VVC. Ibrexafungerp reaches concentrations up to 9-fold higher in vaginal tissues versus plasma. In Phase 2 clinical trials, ibrexafungerp had a clinical cure rate comparable to fluconazole at day 10, but significantly better at day 25. In Phase 3 clinical trials, ibrexafungerp had both a higher clinical and mycologic cure rate versus placebo at both days 10 and 25. In December 2022, Ibrexafungerp received FDA approval for once monthly dosing to decrease the incidence of RVVC. This approval was based on data from the CANDLE STUDY, which showed 65.4% resolution of symptoms and culture negative success through week 24, compared to 53.1% of placebo. Ibrexafungerp provides an alternative oral option for treatment of acute, severe VVC. It is the only FDA approved antifungal for RVVC. Currently, the population likely to benefit from this drug are those with azole allergy, non-albicans or azole resistant albicans species, or other azole contraindications such as drug interactions (like statins or tricyclics). Side effects are mostly gastrointestinal and mild in nature. Ibrexafungerp, like fluconazole, should be used with caution in women who are or may become pregnant.
Topics: Pregnancy; Female; Humans; Candidiasis, Vulvovaginal; Fluconazole; Antifungal Agents; Triterpenes; Candida albicans; Azoles; Polyenes
PubMed: 36785761
DOI: 10.2147/DDDT.S339349 -
Journal of the American Chemical Society Mar 2018A sulfenium-ion-initiated, catalytic, enantioselective polyene cyclization is described. Homogeranylarenes and ortho-geranylphenols undergo polycyclization in good...
A sulfenium-ion-initiated, catalytic, enantioselective polyene cyclization is described. Homogeranylarenes and ortho-geranylphenols undergo polycyclization in good yield, diastereoselectivity, and enantioselectivity. The stereodetermining step is the generation of an enantiomerically enriched thiiranium ion from a terminal alkene and a sulfenylating agent in the presence of a chiral Lewis basic catalyst. The use of hexafluoroisopropyl alcohol as the solvent is crucial to obtain good yields. The thioether moiety resulting from the reaction can be subsequently transformed into diverse oxygen and carbon functionality postcyclization. The utility of this method is demonstrated by the enantioselective syntheses of (+)-ferruginol and (+)-hinokiol.
Topics: Abietanes; Catalysis; Cyclization; Lewis Bases; Molecular Structure; Polyenes; Stereoisomerism
PubMed: 29509003
DOI: 10.1021/jacs.8b01660 -
Biochimica Et Biophysica Acta.... Feb 2019The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering... (Review)
Review
The incidence of resistant fungal pathogens has been increasing, especially in immuno-compromised people. As such, considerable research has been focused on discovering anti-fungal agents with new mechanisms of action and on optimizing the use of existing agents. In this context, interest in the polyene group of anti-fungals has recently been renewed, since they are known to be effective against a broad spectrum of fungal pathogens that only rarely develop a resistance to them. In the past 10 years considerable efforts have been made to improve their efficacy and, simultaneously, to reduce their toxicity. Knowledge about the basic mechanisms of their action will be of crucial importance to further optimizing their use. The mechanisms of polyene action at the membrane level are reviewed here, focusing primarily on their pore-forming activity and on the resulting osmotic responses of artificial lipid vesicles and different eukaryotic cells.
Topics: Antifungal Agents; Lipids; Membranes, Artificial; Polyenes; Porosity
PubMed: 30458121
DOI: 10.1016/j.bbamem.2018.11.006