Quantum mechanics of particles constrained to spiral curves with application to polyene chains.

CONTEXT: Due to advances in synthesizing lower-dimensional materials, there is the challenge of finding the wave equation that effectively describes quantum particles moving on 1D and 2D domains. Jensen and Koppe and Da Costa independently introduced a confining potential formalism showing that the effective constrained dynamics is subjected to a scalar geometry-induced potential; for the confinement to a curve, the potential depends on the curve's curvature function. METHOD: To characterize the π electrons in polyenes, we follow two approaches. First, we utilize a weakened Coulomb potential associated with a spiral curve. The solution to the Schrödinger equation with Dirichlet boundary conditions yields Bessel functions, and the spectrum is obtained analytically. We employ the particle-in-a-box model in the second approach, incorporating effective mass corrections. The π - π ∗ transitions of polyenes were calculated in good experimental agreement with both approaches, although with different wave functions.

Polyene Antibiotics Physical Chemistry and Their Effect on Lipid Membranes; Impacting Biological Processes and Medical Applications.

This review examined a collection of studies regarding the molecular properties of some polyene antibiotic molecules as well as their properties in solution and in particular environmental conditions. We also looked into the proposed mechanism of action of polyenes, where membrane properties play a crucial role. Given the interest in polyene antibiotics as therapeutic agents, we looked into alternative ways of reducing their collateral toxicity, including semi-synthesis of derivatives and new formulations. We follow with studies on the role of membrane structure and, finally, recent developments regarding the most important clinical applications of these compounds.

Sixty years of Amphotericin B: An Overview of the Main Antifungal Agent Used to Treat Invasive Fungal Infections.

Introduced in the late 1950s, polyenes represent the oldest family of antifungal drugs. The discovery of amphotericin B and its therapeutic uses is considered one of the most important scientific milestones of the twentieth century . Despite its toxic potential, it remains useful in the treatment of invasive fungal diseases owing to its broad spectrum of activity, low resistance rate, and excellent clinical and pharmacological action. The well-reported and defined toxicity of the conventional drug has meant that much attention has been paid to the development of new products that could minimize this effect. As a result, lipid-based formulations of amphotericin B have emerged and, even keeping the active principle in common, present distinct characteristics that may influence therapeutic results. This study presents an overview of the pharmacological properties of the different formulations for systemic use of amphotericin B available for the treatment of invasive fungal infections, highlighting the characteristics related to their chemical, pharmacokinetic structures, drug-target interactions, stability, and others, and points out the most relevant aspects for clinical practice.

Nanoparticles as a Tool for Broadening Antifungal Activities.

Fungal infections are diseases that are considered neglected although their infection rates have increased worldwide in the last decades. Thus, since the antifungal arsenal is restricted and many strains have shown resistance, new therapeutic alternatives are necessary. Nanoparticles are considered important alternatives to promote drug delivery. In this sense, the objective of the present study was to evaluate the contributions of newly developed nanoparticles to the treatment of fungal infections. Studies have shown that nanoparticles generally improve the biopharmaceutical and pharmacokinetic characteristics of antifungals, which is reflected in a greater pharmacodynamic potential and lower toxicity, as well as the possibility of prolonged action. It also offers the proposition of new routes of administration. Nanotechnology is known to contribute to a new drug delivery system, not only for the control of infectious diseases but for various other diseases as well. In recent years, several studies have emphasized its application in infectious diseases, presenting better alternatives for the treatment of fungal infections.

The Diversity of Linear Conjugated Polyenes and Colours in Nature: Raman Spectroscopy as a Diagnostic Tool.

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.

Impairment of mixed melanin-based pigmentation in parrots.

Parrots and allies (Order Psittaciformes) have evolved an exclusive capacity to synthesize polyene pigments called psittacofulvins at feather follicles, which allows them to produce a striking diversity of pigmentation phenotypes. Melanins are polymers constituting the most abundant pigments in animals, and the sulphurated form (pheomelanin) produces colors that are similar to those produced by psittacofulvins. However, the differential contribution of these pigments to psittaciform phenotypic diversity has not been investigated. Given the color redundancy, and physiological limitations associated with pheomelanin synthesis, we hypothesized that the latter would be avoided by psittaciform birds. Here, we tested this using Raman spectroscopy to identify pigments in feathers exhibiting colors suspected of being produced by pheomelanin (i.e. dull red, yellow, greyish-brown and greenish-brown) in 26 species from the three main lineages of Psittaciformes. We detected the non-sulphurated melanin form (eumelanin) in black, grey and brown plumage patches, and psittacofulvins in red, yellow and green patches, but there was no evidence of pheomelanin. As natural melanins are assumed to be composed of eumelanin and pheomelanin in varying ratios, our results represent the first report of impairment of mixed melanin-based pigmentation in animals. Given that psittaciforms also avoid the uptake of circulating carotenoid pigments, these birds seem to have evolved a capacity to avoid functional redundancy between pigments, likely by regulating follicular gene expression. Our study provides the first vibrational characterization of different psittacofulvin-based colors and thus helps to determine the relative polyene chain length in these pigments, which is related to their antireductant protection activity.

Antifúngicos poliénicos. Mecanismo de acción y aplicaciones / Polyenic Antifungals. Action Mechanisms and their Applications

Resumen: Los primeros compuestos con actividad antifúngica específica fueron identificados a mediados del siglo pasado como un producto del metabolismo secundario de bacterias del orden Actinomycetales, y su uso en la clínica redujo de manera importante la morbilidad y la mortalidad relacionadas con infecciones severas por hongos de varios géneros. Muchos de estos compuestos biosintéticos se caracterizan por tener una estructura química de tipo poliénico, con un número variable de dobles enlaces carbono-carbono. Actualmente, además de los fármacos poliénicos, existe otro tipo de compuestos con actividad antimicótica, como los azoles, que se utilizan con mayor frecuencia y que presentan menor toxicidad en los pacientes; sin embargo, se han documentado casos de falla terapéutica con tales compuestos, por lo que el uso de los poliénicos se ha mantenido como la mejor alternativa en esos casos. El presente trabajo brinda información acerca de las propiedades y las aplicaciones de los antifúngicos poliénicos teniendo como modelo a la anfotericina B.

Abstract The first compounds with specific antifungal activity were identified in the middle of the last century as a product of the secondary metabolism of bacteria of the order Actinomycetales, and their clinical use significantly diminished the morbidity and mortality associated with severe fungal infections. Many of such biosynthetic compounds are characterized by a chemical polygenic structure, with a variable number of carbon-carbon double bonds. Currently, besides polygenic antimycotics, there are other antifungal agents, such as the azole compounds, that have less toxicity in patients; however, cases of therapeutic failure with such compounds have been documented, therefore, the use of polygenics is still the best alternative in such cases. This review presents data about the properties and applications of antifungal-polygenic compounds using amphotericin B as a model.

Impairment of mixed melanin-based pigmentation in parrots.

Parrots and allies (Order Psittaciformes) have evolved an exclusive capacity to synthesize polyene pigments called psittacofulvins at feather follicles, which allows them to produce a striking diversity of pigmentation phenotypes. Melanins are polymers constituting the most abundant pigments in animals, and the sulphurated form (pheomelanin) produces colors that are similar to those produced by psittacofulvins. However, the differential contribution of these pigments to psittaciform phenotypic diversity has not been investigated. Given the color redundancy, and physiological limitations associated to pheomelanin synthesis, we hypothesized that the latter would be avoided by psittaciform birds. Here we test this by using Raman spectroscopy to identify pigments in feathers exhibiting colors suspicious of being produced by pheomelanin (i.e., dull red, yellow and grey- and green-brownish) in 26 species from the three main lineages of Psittaciformes. We detected the non-sulphurated melanin form (eumelanin) in black, grey and brown plumage patches, and psittacofulvins in red, yellow and green patches, but no evidence of pheomelanin. As natural melanins are assumed to be composed of eumelanin and pheomelanin in varying ratios, our results represent the first report of impairment of mixed melanin-based pigmentation in animals. Given that psittaciforms also avoid the uptake of circulating carotenoid pigments, these birds seem to have evolved a capacity to avoid functional redundancy between pigments, likely by regulating follicular gene expression. Ours study provides the first vibrational characterization of different psittacofulvin-based colors and thus helps to determine the relative polyene chain length in these pigments, which is related to their antireductant protection activity.

Novel antifungal agents: a patent review (2013 - present).

INTRODUCTION: Superficial infections involving the skin and mucosa are the most common fungal disease in humans. Fungi can also produce invasive infections (IFI), which are increasing in incidence among the growing population of immunocompromised patients, and are characterized by a high mortality rate. Amphotericin B, new triazoles and echinocandins have improved treatment options in IFI. However, the frequency of less common and more resistant fungi, the limited activity of available antifungal drugs and their undesirable side effects reflect the urgent need for the development of new therapeutic strategies. Areas covered: This review summarizes the patents granted from August 2013 to June 2016 for antifungal compounds, reflecting the advances made by pharmaceutical companies and research groups in the discovery of new natural or synthetic antifungal compounds as well as the improvement of previously patented structures with antifungal activity. Expert opinion: in the period covered here, progress has been in the development of new antifungal compounds or analogs of existing drugs with broad spectrum of activity, more favorable pharmacokinetic profiles or better bioavailability. However, the development of more promising approaches as antifungal compounds with broader antifungal activity and fungal-specific mechanisms of action are a high priority.

Conjugated polyenes as chemical probes of life signature: use of Raman spectroscopy to differentiate polyenic pigments.

Polyenes, which are represented by carotenes, carotenoids and conjugated polyenals, are some of the most important targets for astrobiology, because they can provide strong evidence of the presence of organic compounds in the most extreme environments, such as on Mars. Raman spectroscopy has been used as the main analytical tool in the identification of such compounds, for the greatest variety of living species, from microorganisms to animals and plants. However, using only the position of the characteristic Raman bands can lead to errors in tentatively identifying chemicals. In this work, we present a series of observations that can provide a more complete and robust way to analyse the Raman spectrum of a polyenal, in which the position, the intensity, the use of various laser lines for excitation, and the combination of more than one pigment can be considered in the complete analysis.

Raman spectroscopy as a tool for polyunsaturated compound characterization in gastropod and limnic terrestrial shell specimens.

The colours of mollusc shells were determined using the Raman spectroscopy and these analyses suggest that the conjugated polyenes (carotenoids) and psittacofulvins are the organic pigments incorporated into their skeletal structures responsible by their colorations. The symmetric stretching vibration of the carbonate ion gives rise to a very strong Raman band at ca. 1089 cm(-1) and a weak band at 705 cm(-1), for all samples; the second band characterizes the aragonite as the inorganic matrix and can be used as a marker. The specimens show bands at 1523-1500 and at 1130-1119 cm(-1), assigned to the ν1 and ν2 modes of the polyenic chain vibrations, respectively. Another band at 1293 cm(-1), assigned to the CH=CH in-plane rocking mode of the olefinic hydrogen is also observed in all samples, which reinforces the psittacofulvin compound as the main pigment present in the analyzed samples.