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5-(2-Aminopropyl)benzofuran (5-APB), also known as “Benzo Fury,” is a novel psychoactive substance (NPS) belonging to a new class of synthetic phenethylamines. It acts by disrupting serotonergic circuits as a serotonin–norepinephrine–dopamine reuptake inhibitor and is classified as an entactogen, similar to MDMA and MDA. Despite its popularity among users, recent toxicity events have been associated with the consumption of 5-APB and other benzofurans, highlighting the need for a better understanding of their pharmacodynamics and toxicity. One way to achieve this is by developing the synthesis of 5-APB metabolites as biomarkers of exposure. In this study, we present a six-step synthesis for one of the 5-APB metabolites, 2-(5-(2-aminopropyl)-2-hydroxyphenyl)acetic acid (1), involving methylation, formylation, Aldol-type condensation, reduction, and hydrolysis reactions. The compound was obtained in an overall yield of 11%.

Summary: Calonectria hemileiae, a fungus associated with pustules of the coffee leaf rust (CLR, Hemileia vastatrix) in Brazil, was tested in vitro and in planta to assess its biocontrol potential. The fungus inhibited the germination of rust spores by over 80%. CLR severity was reduced by 93% when Calonectria was applied to coffee leaf discs inoculated with H. vastatrix, whilst a reduction of 70-90% was obtained for in planta experiments. Mycoparasitism was demonstrated through the fulfillment of Koch's postulates. Elucidation of the biochemical interaction between Calonectria and Hemileia on coffee plants indicated that the mycoparasite was able to increase plant resistance to rust infection. Coffee plants sprayed with Calonectria alone showed greater levels of chitinase, β-1,3-glucanase, ascorbate peroxidase and peroxidase. Although effective in controlling the rust, fungicide applications damaged coffee photosynthesis, whereas no harm was caused by Calonectria. We conclude that C. hemileiae shows promise as a biocontrol agent of CLR.

Onychomycosis induced by Candida spp. has several limitations regarding its treatment. Nail lacquers display the potential to overcome these drawbacks by providing therapeutic compliance and increasing local drug bioavailability. Thus, this work aimed to produce a nail lacquer loaded with Amphotericin B (AmB) and evaluate its performance. The AmB-loaded nail lacquer was produced and preliminarily characterized. An AmB quantification method was developed. Stability, drug release, permeability and anti-Candida activity assays were conducted. The analytical method validation met the acceptance criteria. The drug loading efficiency was 100% (0.02 mg/g of total product), whereas the AmB stability was limited to ≅7 days (≅90% remaining). The nail lacquer displayed a drying time of 187 s, non-volatile content of around 20%w/w, water-resistance of approximately 2%w/w of weight loss and satisfactory in vitro adhesion. Moreover, the in vitro antifungal activity against different Candida spp. strains was confirmed. The AmB release and the ex vivo permeability studies revealed that AmB leaves the lacquer and permeates the nail matrix in 47.76 ± 0.07% over 24 h. In conclusion, AmB-loaded nail lacquer shows itself as a promising extemporaneous dosage form with remarkable anti-Candida activity related to onychomycosis.

The present study shows the factors that modulate the photodamage promoted by phenothiazines. Cytochrome c was irradiated with UV light for 120 min, over a pH range from 4.0 to 8.0, in the absence and in the presence of different concentrations of thioridazine (TR) and fluphenazine (FP). In the absence of phenothiazines, the maximal rate of a Soret band blue shift (nm/min) from 409 to 406 nm was obtained at pH 4.0 (0.028 nm/min). The presence of phenothiazines at the concentration range 10-25 µmol/L amplified and accelerated a cytochrome c blue shift (409 to 405 nm, at a rate = 0.041 nm/min). Above 25 µmol/L, crescent concentrations of phenothiazines contributed to cytochrome c protection with (maximal at 2500 µmol/L). Scanning electronic microscopy revealed the formation of nanostructures. The pH also influenced the effect of low phenothiazine concentrations on cytochrome c. Thus, the predominance of phenothiazine-promoted cytochrome c damage or protection depends on a balance of the following factors: the yield of photo-generated drug cation radicals, which is favored by acidic pH; the stability of the cation radicals, which is favored by the drug aggregation; and the cytochrome c structure, modulated by the pH.