Cryptococcosis is a fungal infection caused mainly by the pathogenic yeasts Cryptococcus neoformans and Cryptococcus gattii . The infection initiates with the inhalation of propagules that are then deposited in the lungs. If not properly treated, cryptococci cells can disseminate and reach the central nervous system. The current recommended treatment for cryptococcosis employs a three-stage regimen, with the administration of amphotericin B, flucytosine and fluconazole. Although effective, these drugs are often unavailable worldwide, can lead to resistance development, and may display toxic effects on the patients. Thus, new drugs for cryptococcosis treatment are needed. Recently, an iridoid named plumieridine was found in Allamanda polyantha seed extract; it exhibited antifungal activity against C. neoformans with a MIC of 250 μg/mL. To address the mode of action of plumieridine, several in silico and in vitro experiments were performed. Through a ligand-based a virtual screening approach, chitinases were identified as potential targets. Confirmatory in vitro assays showed that C. neoformans cell-free supernatant incubated with plumieridine displayed reduced chitinase activity, while chitinolytic activity was not inhibited in the insoluble cell fraction. Additionally, confocal microscopy revealed changes in the distribution of chitooligomers in the cryptococcal cell wall, from a polarized to a diffuse cell pattern state. Remarkably, further assays have shown that plumieridine can also inhibit the chitinolytic activity from the supernatant and cell-free extracts of bacteria, insect and mouse-derived macrophage cells (J774.A1). Together, our results suggest that plumieridine can be a broad-spectrum chitinase inhibitor.

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The rapid development of multidrug-resistant pathogens against conventional antibiotics is a global public health problem. The irrational use of antibiotics has promoted therapeutic limitations against different infections, making research of new molecules that can be applied to treat infections necessary. Antimicrobial peptides (AMPs) are a class of promising antibiotic molecules as they present broad action spectrum, potent activity, and do not easily induce resistance. Several AMPs from scorpion venoms have been described as a potential source for the development of new drugs; however, some limitations to their application are also observed. Here, we describe strategies used in several approaches to optimize scorpion AMPs, addressing their primary sequence, biotechnological potential, and characteristics that should be considered when developing an AMP derived from scorpion venoms. In addition, this review may contribute towards improving the understanding of rationally designing new molecules, targeting functional AMPs that may have a therapeutic application.

The concept of “one target, one drug, one disease” is not always true, as compounds with previously described therapeutic applications can be useful to treat other maladies. For example, acridine derivatives have several potential therapeutic applications. In this way, identifying new potential targets for available drugs is crucial for the rational management of diseases. Computational methodologies are interesting tools in this field, as they use rational and direct methods. Thus, this study focused on identifying other rational targets for acridine derivatives by employing inverse virtual screening (IVS). This analysis revealed that chitinase enzymes can be potential targets for these compounds. Subsequently, we coupled molecular docking consensus analysis to screen the best chitinase inhibitor among acridine derivatives. We observed that 3 compounds displayed potential enhanced activity as fungal chitinase inhibitors, showing that compound 5 is the most active molecule, with an IC50 of 0.6 ng/µL. In addition, this compound demonstrated a good interaction with the active site of chitinases from Aspergillus fumigatus and Trichoderma harzianum. Additionally, molecular dynamics and free energy demonstrated complex stability for compound 5. Therefore, this study recommends IVS as a powerful tool for drug development. The potential applications are highlighted as this is the first report of spiro-acridine derivatives acting as chitinase inhibitors that can be potentially used as antifungal and antibacterial candidates.

O aumento do consumo sustentável na cosmetologia tem desencadeado um maior uso de matérias-primas naturais para o desenvolvimento de formulações. Os óleos vegetais contêm ácidos graxos fundamentais para o organismo. O objetivo deste trabalho é executar uma prospecção tecnológica sobre o uso de ácidos graxos dos óleos vegetais na cosmetologia. Foram usados os bancos de dados EPO, WIPO, INPI, LENS e Google Patents, com as palavras-chave “Ácidos Graxos Óleos Vegetais/Fatty Acids Vegetable Oils”, “Cosméticos Óleos Vegetais/Cosmetics Vegetable Oils” e “Cosméticos Ácidos Graxos/Cosmetics Fatty Acids”. O Instituto Nacional da Propriedade Industrial (INPI) apresentou o menor número de depósitos de patentes, já o LENS teve o maior número de patentes. O cenário internacional aparenta mais investimentos. Já o Brasil precisa de mais estímulos para alcançar mais avanços nessa área de estudo. Além disso, o país deve utilizar seus recursos naturais como um diferencial competitivo em meio ao mercado nacional e internacional.