A 3-alkylpyridine-bearing alkaloid exhibits potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with no detectable resistance.

Staphylococcus aureus is a Gram-positive bacterium responsible for a wide variety of infectious diseases, and its methicillin-resistant isolates pose a serious worldwide public health risk. New drugs are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA and, of these compounds, compound 6 showed promising antibacterial activity against Staphylococcus with minimum inhibitory concentration (MIC) ranging from 0.98 to 3.9 µgmL-¹ . In addition, it exhibited a rapid bactericidal action, with complete elimination of MRSA after 6 h of incubation at 15.6 µgmL-¹ . Compound 6 had the ability to damage the bacterial membrane and induce cell lysis and, due to its action on the membrane, showed low resistance induction potential in vitro. In the combination study, compound 6 revealed an additive effect (FICI = 1) with vancomycin and ofloxacin and ciprofloxacin (FICI = 0.75) against MRSA, reducing the effective concentration of this antibiotic two-fold. The anti-staphylococcal activity of compound 6 was stable in the presence of different concentrations of NaCl (50, 200, and 400 µM), trypsin ( 1:500, 1:250) and under a variety of pH values (4, 5, 6, and 8); however, its binding to plasmatic proteins (i.e., albumin) was substantial. The previous exposure of MRSA to the compound was able to reduce the formation of bacterial biofilm and reduce the biomass of mature biofilms. Compound 6 showed low selectivity in vitro for MRSA USA 300 when compared to eukaryotic cells (epithelial, fibroblast, and red blood cells).

Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids.

Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 µg/mL and MFC 62.5 µg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 µg/mL), and C. tropicalis (MIC 31.2 µg/mL and MFC 125 µg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.

Official labeled and unlabeled Brazilian honey. Comparison between physicochemical, microbiological, and microscopic parameters / Miel brasileña oficial etiquetada y no etiquetada. Comparación entre parámetros fisicoquímicos, microbiológicos y microscópicos / Mel brasileiro oficialmente rotulado e não rotulado. Comparação entre parâmetros físico-químicos, microbiológicos e microscópicos

SUMMARY Introduction: Honey is a natural substance produced by bees mainly from flower nectar with high nutritional value. However, many commercialized samples are adulterated or falsified. Method: We bought twelve honey samples in markets in the city of Betim (Brazil) and analyzed their acidity, pH, electrical conductivity, insoluble matter, ashes, moisture content, presence of mesophile bacteria, molds, yeasts, total coliforms, Salmonella spp. and the presence of pollen grains. Results: Considering all honey samples, the average pH was 3.8 ± 0.5 and the average free acidity was 29.8 ± 6.6 mEq/kg. Considering acidity, we found the average of lactonic acidity 6.4 ± 2.4 mEq/kg and a total average acidity of 36.2 ± 6.9 mEq/kg. The average moisture content was 19.4 ± 1.0 %, the average electrical conductivity was 391.6 ± 168.6 μS/ cm, the average amount of ashes was 0.5 ± 0.8 % and the average insoluble matter was 0.08 ± 0.02 %. Only the moisture was significantly different between the two groups and ten honey samples had pollen grains. Conclusions: The quality parameters of the labeled and unlabeled samples were not significantly different, although two samples of unlabeled honey were fraudulent, mainly due to the absence of pollen grains. Identifying the presence or absence of pollen in the samples is a safe, economical, and reliable first step for verifying the authenticity of the honey.

RESUMEN Introducción: La miel es una sustancia natural producida por las abejas, principalmente, a partir del néctar de flores con alto valor nutricional. Sin embargo, muchas muestras comercializadas están adulteradas o falsificadas. Método: Compramos doce mieles en mercados de la ciudad de Betim (Brasil) y analizamos su acidez, pH, conductividad eléctrica, materia insoluble, cenizas, contenido de humedad, presencia de bacterias mesófilas, mohos, levaduras, coliformes totales, Salmonella spp. y la presencia de granos de polen. Resultados: Considerando todas las muestras de miel, el pH promedio fue de 3,8 ± 0,5 y la acidez libre promedio fue de 29,8 ± 6,6 mEq/kg. Considerando la acidez, encontramos el promedio de acidez lactónica 6,4 ± 2,4 mEq/kg y una acidez promedio total de 36,2 ± 6,9 mEq/kg. El contenido de humedad promedio fue 19,4 ± 1,0 %, la conductividad eléctrica promedio fue 391,6 ± 168,6 μS/crn, la cantidad promedio de cenizas fue 0,5 ± 0,8 % y la materia insoluble promedio fue 0,08 ± 0,02 %. Sólo la humedad fue significativamente diferente entre los dos grupos y diez de las muestras de miel tenían granos de polen. Conclusiones: Los parámetros de calidad de las muestras etiquetadas y no etiquetadas no fueron significativamente diferentes, aunque dos muestras de miel no etiquetadas fueron fraudulentas, debido a la ausencia de granos de polen. Identificar la presencia o ausencia de polen en las muestras es un primer paso seguro, económico y confiable para verificar la autenticidad de la miel.

RESUMO Introdução: O mel é uma substância natural produzida pelas abelhas principalmente a partir do néctar da flor com alto valor nutritivo. No entanto, muitas amostras comercializadas são adulteradas ou falsificadas. Método: Compramos doze méis em mercados da cidade de Betim (Brasil) e analisamos sua acidez, pH, condutividade elétrica, sólidos insolúveis, cinzas, teor de umidade, presença de bactérias mesófilas, bolores, leveduras, coliformes totais, Salmonella spp. e a presença de grãos de pólen. Resultados: Considerando todas as amostras de mel, o pH médio foi de 3,8 ± 0,5 e a acidez livre média foi de 29,8 ± 6,6 mEq/kg. Considerando a acidez, encontramos a média de acidez lactô-nica de 6,4 ± 2,4 mEq/kg e uma acidez média total de 36,2 ± 6,9 mEq/kg. O teor de umidade médio foi de 19,4 ± 1,0 %, a condutividade elétrica média foi 391,6 ± 168,6 μS/cm, a quantidade média de cinzas foi 0,5 ± 0,8 % e a matéria insolúvel média foi 0,08 ± 0,02 %. Apenas a umidade foi significativamente diferente entre os dois grupos e dez das amostras de mel apresentaram grãos de pólen. Conclusões: Os parâmetros de qualidade das amostras rotuladas e não rotuladas não foram diferentes, embora duas amostras de mel não rotulado fossem fraudulentas, principalmente devido à ausência de grãos de pólen. Identificar a presença ou ausência de pólen nas amostras é um primeiro passo seguro, económico e confiável para verificar a autenticidade do mel.

Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).

The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19.

Identification of a Potential Zika Virus Inhibitor Targeting NS5 Methyltransferase Using Virtual Screening and Molecular Dynamics Simulations.

The NS5 methyltransferase (MTase) has been reported as an attractive molecular target for antivirals discovery against the Zika virus (ZIKV). Here, we report structure-based virtual screening of 42 390 structures from the Development Therapeutics Program (DTP) AIDS Antiviral Screen Database. Among the docked compounds, ZINC1652386 stood out due to its high affinity for MTase in comparison to the cocrystallized ligand MS2042, which interacts with the Asp146 residue in the MTase binding site by hydrogen bonding. Subsequent molecular dynamics simulations predicted that this compound forms a stable complex with MTase within 50 ns. Thus, ZINC1652386 may represent a promising ZIKV methyltransferase inhibitor.

Identification of Zika Virus NS2B-NS3 Protease Inhibitors by Structure-Based Virtual Screening and Drug Repurposing Approaches.

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I ) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important amino acid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in Vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of 69.0 ± 7.3 µM and SI = 1.9), and explicit molecular dynamics simulations implemented on a NAMD program indicated great stability of chlorcyclizine in protease binding site, suggesting the repurposing of chlorcyclizine as a promising finding in anti-ZIKV drug development.

Design, synthesis, biological activity and structure-activity relationship studies of chalcone derivatives as potential anti-Candida agents.

Vulvovaginal candidiasis (VVC) affects millions of women around the world every year. Candida albicans is the most frequently isolated pathogen in women and its rapid ability to develop resistance to first and second line therapies has boosted the search for new and effective antifungal agents. In this study, we show the in vitro anti-Candida activity of fifteen synthetic chalcone analogs and their antifungal potential in an in vivo model of VVC. Chalcone 12 showed potent antifungal effects, being able to inhibit the growth of Candida spp. at a concentration of 15.6 µg mL-1. In addition, mechanism of action studies have indicated the ergosterol fungal membrane as the target of this compound. Despite a considerable antifungal activity, the chalcone 12 showed high cytotoxicity in kidney cells lineages. Moreover, this compound was able to reduce Candida-associated virulence, impairing yeast-hyphal transition in C. albicans. An in vivo model of VVC showed that chalcone 12 significantly reduces the fungal load. Taken together, these findings showed that the chalcone 12 is a potent anti-Candida agent in vitro beyond of contribute to improve the fungal infection in a model of CVV. However, it showed low selectivity and high toxicity, suggesting molecular modifications to minimize these proprieties.