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At least 289 records · Page 16Linked to original sources
PubMed2006

Significant improvement of antifungal activity of polyene macrolides by bisalkylation of the mycosamine.

[reaction: see text] New derivatives of Amphotericin B (AmB) were synthesized through a double reductive alkylation of the mycosamine. These derivatives of AmB displayed superior antifungal activity against Saccharomyces cerevisiae wild-type strain and especially in the case of an AmB-resistant Candida albicans strain. Moreover, these compounds are potential drug candidates because of significantly reduced hemotoxicity compared to AmB. Furthermore, the same mycosamine modification can be applied to other polyene macrolides such as Nystatin and Pimaricin to improve their antifungal activity.

Alkylation↗
PubMed2003

Novel polyene dyes for highly efficient dye-sensitized solar cells.

We have developed an efficient and novel polyene-dye-sensitized nanocrystalline TiO2 solar cells producing a 6.8% solar energy-to-electricity conversion efficiency (eta) under AM 1.5 irradiation (100 mW cm(-2)): short-circuit current density (Jsc), 12.9 mA cm(-2), open-circuit photovoltage (Voc), 0.71 V, fill factor (ff), 0.74.

Coloring Agents↗
PubMed2003

Biomimetic studies on polyenes.

The crispatenes and SNF4435 C&D are complex polypropionate derived natural products. The core structures of these compounds along with a complex unnatural structure can be easily prepared from a common polyene precursor simply by variation of the reaction conditions. The reaction pathways provide insight into the biosynthesis of these complex natural products.

Magnetic Resonance Spectroscopy↗
PubMed2003

Photoexcited breathers in conjugated polyenes: an excited-state molecular dynamics study.

pi-conjugated polymers have become an important class of materials for electronic devices. Design of these devices requires understanding such processes as photochemical reactions, spatial dynamics of photoexcitations, and energy and charge transport, which in turn involve complex coupled electron-vibrational dynamics. Here we study nonlinear photoexcitation dynamics in the polyene oligomers by using a quantum-chemical method suitable for the simulation of excited-state molecular dynamics in extended molecular systems with sizes up to hundreds of atoms. The method is based on the adiabatic propagation of the ground-state and transition single-electron density matrices along the trajectory. The simulations reveal formation of a self-localized vibronic excitation ("breather" or multiquanta bound state) with a typical period of 34 fs and allows us to identify specific slow and fast nuclear motions strongly coupled to the electronic degrees of freedom. The effect of chain imperfections and chemical defects on the dynamics is also investigated. A complementary two-dimensional analysis of corresponding transition density matrices provides an efficient way to monitor time-dependent real-space localization of the photoexcitation by identifying the underlying changes in charge densities and bond orders. Possible correlated electronic and vibrational spectroscopic signatures of photoexcited breathers are predicted, and generalizations to energy localization in complex macromolecules are discussed.

Algorithms↗
PubMed1972

Fluorescence studies of the binding of the polyene antibiotics filipin 3, amphotericin B, nystatin, and lagosin to cholesterol.

The interactions of filipin III, amphotericin B, nystatin, and lagosin with sterols in aqueous suspension and in vesicles were followed by fluorescence excitation spectra and by measurement of polarized fluorescence intensities. The equilibrium constants for association of the polyene antibiotics with aqueous suspensions of cholesterol follow the order filipin III > amphotericin B > nystatin > lagosin, in agreement with the order reported for the extent of damage these antibiotics cause in natural and model membranes. Fluorescence polarization measurements show that hydrophobic forces are primarily responsible for the formation of the complexes. Filipin III undergoes a large enhancement in fluorescence polarization on binding to aqueous suspensions of cholesterol and epi-cholesterol, and to vesicles of lecithin-cholesterol, lecithin-beta-cholestanol, and lecithinergosterol. Small increases in polarization occur on interaction of filipin III with vesicles derived from lecithin and epi-cholesterol, thiocholesterol, and androstan-3beta-ol. Amphotericin B undergoes a relatively constant enhancement in fluorescence polarization on interaction with the various lecithin-sterol vesicles used and does not display the selectivity exhibited by filipin III. It is suggested that filipin III serves as a probe of lecithin-sterol interaction.

Amphotericin B↗
PubMed1995

Long-chain polyene status of preterm infants with regard to the fatty acid composition of their diet: comparison between absolute and relative fatty acid levels in plasma and erythrocyte phospholipids.

The long-chain polyene (LCP) status of thirty-nine premature infants (birth weight < 1800 g) was evaluated. Twenty-seven infants were fed on an artificial formula, twelve received their own mother's breast milk. Fatty acid compositions of both plasma and erythrocyte (RBC) phospholipids (PL) were determined in umbilical venous blood and in weekly postnatal blood samples until the 28th day of life. Individual fatty acid levels were expressed as absolute quantities (mg fatty acid/l plasma or RBC suspension) and as relative (mg/100 mg total fatty acids) values. The changes with time in the absolute values for 22:6n-3 and 20:4n-6 in plasma were strikingly different from those of the relative values for these fatty acids. In plasma PL the inter-group differences in the absolute postnatal values for 22:6n-3 (P < 0.0005) and 20:4n-6 (P < 0.05) and the relative values for 22:6n-3 (P < 0.02) were significant, with lower fatty acid values in the formula-fed infants. In RBC PL, no significant inter-group differences in the postnatal 22:6n-3 and 20:4n-6 values were found. Based on the assumption that it is desirable for formula-fed infants to achieve postnatal plasma LCP values at least comparable with those found in infants fed on human milk, the findings of the present study indicate that both n-3 and n-6 LCP should be added to preterm infant formulas. Moreover, the additional importance of absolute fatty acid levels was demonstrated, although analytical procedures need to be standardized to enable effective comparison of results from different research groups.

Dietary Fats↗
PubMed2006

Triazole-polyene antagonism in experimental invasive pulmonary aspergillosis: in vitro and in vivo correlation.

Combination antifungal therapy is increasingly used in the treatment of invasive aspergillosis. Whether the interaction between amphotericin B and triazoles is antagonistic against invasive aspergillosis is a controversial issue that is not likely to be resolved through a randomized clinical trial. Here, we found both in vitro and in vivo antagonism between liposomal amphotericin B and ravuconazole in simultaneous treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits. Bliss independence-based drug-interaction modeling showed significant antagonism in vitro and in vivo, with the observed drug effects being 20%-69% lower than would be expected if the drugs were acting independently. These in vitro and in vivo findings of antagonism were consistent with the findings from Loewe additivity-based drug-interaction modeling. No pharmacokinetic interaction was found. The combination of a triazole and polyene may be antagonistic in the treatment of invasive pulmonary aspergillosis.

Amphotericin B↗
PubMed1986

Suggested mechanisms for the antimycotic activity of the polyene antibiotics and the N-substituted imidazoles.

The polyene antibiotics and the N-substituted imidazoles (azoles) are two groups of clinically important antifungal drugs. Both are hydrophobic and both interact with the plasma membrane of susceptible fungi but the mode of action of the two groups is not fully resolved. In this paper their biological properties are reviewed in the context of recent work so that common features may be identified and further areas of research indicated.

Amphotericin B↗
PubMed2000

Anticandidal activity of SPA-S-843, a new polyenic drug.

The activity of a new, soluble and stable polyene (SPA-S-843) against Candida albicans was assessed by contact and culture tests and by inhibition of germ-tube formation. The drug demonstrated a higher contact activity and lower MICs than amphotericin B. This antimicrobial activity was more evident under acid pH and low ionic strength. In addition, the ability of SPA-S-843 to inhibit Candida sp. conversion from yeast to mycelial form was evident at low drug concentrations (0.25-0.62 mg/L).

Amphotericin B↗
PubMed2002

The use of lipid emulsions for the i.v. administration of a new water soluble polyene antibiotic, SPK-843.

Venous tolerance of a new water soluble polyene antibiotic, SPK-843, in 5% glucose solution for infusion is low in laboratory animals. The use of Intralipid 10% emulsion was therefore proposed, in which the antibiotic remained chemically stable for at least 2 h in a mildly acid or nearly neutral environment and at concentrations of 0.1-0.5 mg/mL, producing no alterations in the emulsion structure. Tolerance was assessed through repeated infusions in the ear marginal vein of rabbits and was found much more satisfactory than the tolerance observed when the vehicle used was 5% glucose solution. The study of the effect of some variables (concentration, volume infused, dose per kg) on venous toxicity offered the possibility to plan optimal administration conditions of presumed therapeutic doses.

Animals↗
PubMed2002

In vitro susceptibilities of Zygomycota to polyenes.

The in vitro activity of polyenes was determined for 36 isolates of Zygomycota including Rhizopus spp. (15), Absidia corymbifera (10), Mucor spp. (6), Rhizomucor spp. (3), Cunninghamella bertholletiae (1) and Apophysomyces elegans (1). All isolates were tested with amphotericin B, heated amphotericin B and nystatin by a broth microdilution test. There were no significant differences between heated and unheated solutions of amphotericin B in terms of their antifungal activities. The MICs of amphotericin B for most of the strains were <2 mg/L. For all isolates, nystatin was significantly less active than amphotericin B (P < 0.001). The one C. bertholletiae and one A. elegans isolates were less susceptible to amphotericin B (MICs 2 mg/L) and were also less susceptible to nystatin.

Amphotericin B↗
PubMed2005

Experimental systemic murine aspergillosis: treatment with polyene and caspofungin combination and G-CSF.

OBJECTIVES: In view of the poor therapy outcomes of invasive aspergillosis, the objective of this study was to evaluate the efficacy of combination treatment consisting of the polyene amphotericin-B-intralipid, the echinocandin caspofungin and granulocyte-colony stimulating factor (G-CSF) in experimental murine systemic aspergillosis. With inhibition of synthesis of 1,3-beta-d-glucan in the fungal cell wall by caspofungin and an effect on the cell membrane by amphotericin-B-intralipid, this treatment may result in a synergic effect against Aspergillus fumigatus. Addition of G-CSF may further contribute to therapy of aspergillosis. METHODS: ICR mice were immunosuppressed by intraperitoneal administration of cyclophosphamide. Three days later, the mice were inoculated intravenously (iv) with A. fumigatus conidia. Infection and treatment were evaluated during an observation period of 30 days in terms of mortality (survival rate and mean survival time) and morbidity (quantitative determination of fungal burden, histopathology, and detection of serum galactomannan). RESULTS: Combination of caspofungin + G-CSF or addition of G-CSF to the combination of caspofungin + amphotericin-B-intralipid increased the survival rate of infected mice up to 78.9% and prolonged their mean survival time to 25 days. These combinations also resulted in a reduction in fungal burden in organs, and a decrease in serum galactomannan. CONCLUSIONS: The successful results obtained in the experimental model may possibly open the way to more effective management of aspergillosis in humans.

Amphotericin B↗
PubMed2006

Is there a role for polyenes in treating invasive mycoses?

PURPOSE OF REVIEW: This is a clinical review on the current role of polyene antifungals in the treatment of invasive fungal infections. It is timely and relevant because the number of new antifungals being developed has never been greater than today. In addition to re-examining the landmark clinical trials of the past, the more recent findings are put into perspective. The past year has been particularly rich in clinical trials. RECENT FINDINGS: The main topics of this review are invasive candidiasis, invasive aspergillosis, and the so-called rare fungal infections: zygomycosis, fusariosis, cryptococcosis and histoplasmosis. SUMMARY: Practical implications of the recent developments are the almost complete replacement of amphotericin B deoxycholate by lipid-based formulations; antifungal efficacy without compromising safety; and treatment choices for infections previously considered untreatable.

Amphotericin B↗
PubMed1979

The effects of the polyene antibiotic mepartricin on polymorphonuclear leucocyte function: an in-vitro study.

Mepartricin, a polyene antibiotic with candidacidal and trichomonicidal activity, was found to be without toxic effects for human polymorphonuclear leucocytes; the drug seems to be unable to enter the human cells. Some synergism between the antifungal activities of mepartricin and of human leucocytes is seen if Candida cells are pre-incubated with sub-lethal concentrations of the drug.

Candida↗
PubMed2006

Glycerol, ethylene glycol and propanediol elicit pimaricin biosynthesis in the PI-factor-defective strain Streptomyces natalensis npi287 and increase polyene production in several wild-type actinomycetes.

Production of pimaricin by Streptomyces natalensis ATCC 27448 is elicited by the PI-factor, an autoinducer secreted by the producer strain during the rapid growth phase. Exogenous PI-factor restored pimaricin production in a mutant strain npi287 defective in PI-factor biosynthesis. During purification of the PI-factor, a second pimaricin-inducing fraction different from PI-factor was isolated from the culture broth of wild-type S. natalensis ATCC 27448. After purification by HPLC and analysis by MS and NMR, this active fraction was shown to contain glycerol and lactic acid. Pure glycerol restored pimaricin production in liquid cultures of the autoinducer-defective npi287 mutant. A similar effect was exerted by ethylene glycol, 1,2-propanediol and 1,3-propanediol but not by higher polyalcohols or by glycerol acetate or glycerol lactate esters. Glycerol stimulated (30-270 %) the production of six different polyene macrolide antibiotics by their respective producer strains. Addition of glycerol to the inducer-defective npi287 strain restored pimaricin production but did not result in extracellular or intracellular accumulation of PI-factor. Exogenously added PI-factor was internalized by the cells in the presence of glycerol, and a mixture of both PI-factor and glycerol produced a slightly higher inducing effect on pimaricin production than PI-factor alone. In summary, glycerol, ethylene glycol and propanediol exert a bypass of the PI-factor inducing effect on pimaricin biosynthesis.

Butanols↗
PubMed1977

Effect of the polyene antibiotic filipin on the permeability of the inward- and the outward-facing membranes of the isolated from skin (Rana temporaria).

The effect of the polyene antibiotic filipin on the electrical properties and the passive permeability of the cell membranes was investigated. The addition of filipin to the outside bathing solution has the following effects: 1. it results in a drastic reduction in the transepithelial resistance and potential, 2. it causes a 10-20 times increase in the passive transepithelial chloride, sodium and sucrose flux, 3. it results in the formation of an amiloride insensitive sodium pathway in the outward facing membrane, 4. it results in an active outward transport of potassium, 5. it results in a highly significant swelling of all the cells in the epithelium. The addition of filipin to the inside bathing solution has the following effects 1. it results in an activation of the active sodium transport, 2. it causes a slight increase in the passive transepithelial chloride and sodium permeabilities but has no effect on the sucrose permeability, 3. it has no effect on the amiloride inhibition of the short-circuit current, 4. it has no effect on the volume of the cells in the epithelium. It is suggested that the addition of filipin to the outside bathing solution increases the direct sodium flow from cell to cell in neighbour layers. Furthermore these experiments indicate that the outward facing membrane of the isolated frog skin has a high cholesterol content as compared with the cholesterol content of the inward facing membrane.

Amiloride↗
PubMed1995

Photostationary state compositions of retinal and related compounds included in beta-lactoglobulin. Effects of protein host on isomer distribution of polyene substrates.

The UV-visible absorption spectra and photostationary state compositions of retinal (or the related C-18 ketone, 3-dehydroretinal and the C-22 aldehyde) imbedded in the binding cavity of beta-lactoglobulin (BLG) are consistent with the view that the carbonyl group of these polyenes are hydrogen-bonded with the protein host, most likely with the lone protonated lysine residue in the binding pocket. Patterns of variation in photochemical behavior of the imbedded chromophore versus that in solution are discussed in terms of possible specific protein-substrate interactions. The results are also compared with that of the methyl ether of retinol where similar hydrogen bonding is not possible.

Chemical Phenomena↗
PubMed1990

In vitro activities of polyene and imidazole antifungal agents against unusual opportunistic fungal pathogens.

Guidelines for the treatment of infections caused by unusual opportunistic fungi are limited and available in vitro data are scanty. In vitro susceptibility tests, employing an agar dilution procedure, were performed with amphotericin B (AMB), natamycin (NTC), itraconazole (ICZ), and ketoconazole (KTZ). Two media were used: Kimmig's agar (KA) and Yeast Morphology Agar (YMA). Fungi tested included isolates (n) of Acremonium spp. (10), Cunninghamella spp. (6), Fusarium spp. (18), Pseudallescheria boydii (14), and Trichosporon beigelii (5). All Acremonium and Cunninghamella isolates were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but many appeared to be resistant to AMB, (MIC greater than or equal to 32 micrograms/ml), KTZ and ICZ (MIC greater than or equal to 128 micrograms/ml). Most isolates of Fusarium spp. were susceptible to both AMB and NTC (MIC90 = 4 micrograms/ml); one isolate was cross-resistant to both polyenes (MIC greater than 32 micrograms/ml). Only two of 18 Fusarium isolates appeared susceptible to the imidazoles (MIC less than or equal to 4 micrograms/ml); the remaining isolates exhibited high MICs (greater than or equal to 64 micrograms/ml). All 14 isolates of P. boydii were susceptible to NTC (MIC less than or equal to 4 micrograms/ml) but four appeared to be resistant to AMB (MIC greater than or equal to 32 micrograms/ml). Most isolates of P. boydii were susceptible to both KTZ (MIC less than or equal to 4 micrograms/ml) and ICZ (MIC less than or equal to 16 micrograms/ml) but two isolates appeared to be resistant (MIC greater than or equal to 16 micrograms/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Antifungal Agents↗