Introduction: This increase in the prevalence of drug-resistant pathogens occurs at a time when the discovery and development of new antimicrobial agents occur slowly. In this context, the objective of this study was to investigate the antifungal activity of isoeugenol, a phenylpropanoid, by in vitro and in silico assays against Penicillium citrinum strains. Material and Method: For in silico analysis, the software PASS online, Molinspiration and Osíris were used. For the determination of Minimum Inhibitory Concentration (MIC) and Minimal Fungicide Concentration (MFC) of isoeugenol and voriconazole were carried out using the broth microdilution technique. PASS online has shown that isoeugenol has the opportunity to present antiseptic, antifungal, antibacterial, antimycobacterial activities. Molinspiration showed that the phytoconstituent has good potential for oral bioavailability. Conclusion: In the analysis with the Osiris program, it was demonstrated that isoeugenol has low irritant and tumorigenic risk. The MIC of isoeugenol varied between 256 and 32 µg/mL, MIC50 of 64 µg/mL and MIC90 was 128 µg/mL. The MFC50, MFC90 and MFC of the isoeugenol for P. citrinum species were 64, 256 and 518 μg/mL, respectively. After analysis, it was verified that the isoeugenol have bactericidal effect against the strains of P. citrinum. After these results, it is important to discover the mechanism of action involved in the antifungal action of the compound, as well as in vitro and in vivo toxicity tests.

Este trabalho propôs - se diagnosticar e analisar o sistema de gerenciamento dos resíduos sólidos hospitalares da cidade de Campina Grande, verificando a importância que os hospitais dispensam não só ao manejo como também a preservação do ambiente em que eles atuam. A falta de uma iniciativa concreta de reciclar algum resíduo das unidades hospitalares, está intimamente ligada à inexistência de um modelo adequado para o manejo. A ocorrência de 35,71% de hospitais utilizando o modelo da ABNT sem nenhuma reciclagem de resíduo, acusa a possibilidade da falta de atenção e importância dedicada aos aspectos de reaproveitamento de resíduos gerados.Pela a análise realizada, constatou-se que o envolvimento ambiental do setor hospitalar da cidade de Campina Grande deixa a desejar de acordo com a legislação vigente no Brasil, relacionado aos impactos negativos gerados a sociedade e ao meio ambiente. A iniciativa privada exerce uma forte influência na perspectiva hospitalar de Campina Grande por responder por 71,4% da amostra pesquisada, o que concede a esse setor uma forte sensibilidade nos resultados gerais. A situação apontada torna-se ainda mais preocupante, na medida em que os hospitais não investem contundentemente recursos para a minimização do "gapâ€? entre o pouco conhecimento dos funcionários a respeito dos riscos e a real necessidade e profundidade desse conhecimento.

The antifungal therapy combined is used in clinical practice of several mycoses as it may increase the efficacy of the treatment. The use of natural products (phytochemicals) in combination with conventional antifungal drugs has been related to beneficial effects, mainly synergistic effects. The aim of this study was to evaluate the effect of the combined use of eugenol / isoeugenol, compounds with recognized antimicrobial activity, in association with antifungal amphotericin B against strains of Cryptococcus neoformans. The combined antifungal effect were be determined from the Fraction Inhibitory Concentration index - checkerboard technique. The results obtained in this study showed that eugenol in combination with amphotericin B had antagonistic effect against the strains of C. neoformans, LM 615 and INCQS 40221 (FIC index 6.0 and 4.0), respectively. The combination of the isoeugenol and amphotericin B also showed antagonistic effects for both the LM 615 strain and INCQS 40221 (FIC index 6.0 and 5.0), respectively. This study contributed to the understanding of the antifungal effects of the association of phenylpropanoids (eugenol / isoeugenol) with amphotericin B. Further studies are needed to evaluate and compare the effects of the association of these phytochemicals with other conventional antifungal drugs used against C. neoformans.

Graphical AbstractAbstract.Human mycoses have controversial treatment, since the available antifungal drugs besides favoring the appearance of resistant isolates, can present great toxicity to the human organism. This fact has driven the search for more efficient, safe and natural therapeutic alternatives with the objective of reversing this scenario of resistance presented by pathogenic fungi, for this, new natural and effective alternatives, such as the use of plant extracts, natural compounds and semisynthetic, have been extensively investigated for the development of new drugs. In view of this scenario, this study aims to evaluate the antifungal activity of isoeugenol in vitro against strains of Penicillium citrinum. For this, the broth microdilution technique was used to determine the Minimum Inhibitory Concentration (MIC) and Minimum Fungicide Concentration (MFC) of isoeugenol and voriconazole. The concentrations by which the strains were submitted, 1024 μg/mL to 0.5 μg/mL, were obtained by means of serial dilution at a ratio of two, so that in the first row of the plate is the highest concentration and in the last , the lowest concentration. Finally, 10 μL of the fungal inoculum of each isolate was added to the wells, where each strain was placed on a plate MOL2NET, 2017, 3, doi:10.3390/mol2net-03-xxxx 2 column. MIC was defined as the lowest concentration capable of inhibiting fungal growth visually verified by maintaining the original coloration of the medium. After reading the MIC, aliquots of 20 μL of the supernatant from the wells where complete inhibition of fungal growth in the microdilution plates were observed were plated on Sabouraud dextrose agar plates. Plates were incubated, and MFC was considered the lowest concentration at which growth was less than 3 colonies. The assays were performed in triplicate and the geometric mean was calculated. The CIM of isoeugenol varied between 256 and 32 μg/mL, being the highest MIC value for the LM-21 strain and the lowest value for the LM-02, LM-03, LM-08, LM-155, LM-157 and LM-161. The MIC range of voriconazole was 0.5 to 256 μg/mL. The MFC of isoeugenol varied between 64-512 μg/mL and for voriconazole it was 2 μg/mL and above 1024 μg/mL. In this way, we can conclude that isoeugenol presented an antifungal effect, which enables it as a potential antifungal drug, requiring complementary tests that clarify the mechanism of action involved in its antimicrobial activity.

Abstract.The search for new compounds with antifungal activity has become very important, mainly due to the large increase of fungal infections and also the appearance of antifungal resistant strains available in the market, as well as for use for pest control. Medicinal plants represent an alternative for the substitution of these synthetic fungicides for natural products, since they have a large quantity and variety of secondary metabolites with biological properties, among them, phenylpropanoids. Therefore, the present study aims to investigate the in silico antimicrobial and toxicological potential of 2-Methoxy-4-propenylphenol (isoeugenol) through computational analysis. For this, the Prediction of Activity Spectra for Substances (PASS online), Molinspiration and Osiris software were used. PASS online showed that isoeugenol has the opportunity to present antiseptic (Pa: 0.571 and Pi: 0.009), antifungal (Pa: 0.492 and Pi: 0.032), antibacterial (Pa: 0.379 and Pi: 0.035), antimycobacterial (Pa: and Pi: 0.022) and antihelmintic (Pa: 0.335 and Pi: 0.028), mainly against nematoda (Pi: 0.562 and Pa: 0.009). Molinspiration showed that the phytoconstituent has good potential for oral bioavailability, with nDLH = 1, nALH = 2, mass = 164.2 Da and MOL2NET, 2017, 3, doi:10.3390/mol2net-03-xxxx 2 cLogP = 2.38. In the analysis with the Osiris program, it was demonstrated that isoeugenol has low irritant (1) and tumorigenic risk (1), and high mutagenic risk and high reproductive toxicity. In view of this instilled study, it was possible to verify that the compound is a potential candidate for in vitro and in vivo studies of antimicrobial and toxicological action and to prove the data obtained from the computational analysis. IntroductionThe occurrence of antifungal resistance cases used in clinical practice has made the search for new molecules with potential biological activity increasingly subject to studies related to antimicrobial activity [1][2]. Thus, the search for new substances capable of combating fungal infections, or even improving the action of antifungal agents commonly used in the clinic, may be a promising path to fight against resistance and reduce the limitations of conventional treatment, such as adverse effects and high toxicity [3], not only in human use, but also in pest control in agriculture.Alternatively, we have plants as sources of new biologically active compounds. The great quantity and diversity of secondary plant metabolites has been attracting the interest of researchers from different areas of science, who see in plants a promising source for the discovery of molecules with potential human use, with significant commercial value in the pharmaceutical, food, agronomic and cosmetic [4]. These studies are important for the discovery of compounds with biological activities, since their structural diversity of these substances is greater than that presented by most of the combinatorial strategies carried out on heterocyclic compounds [5]. These characteristics give these compounds a grea...