Neurotoxic and behavioral deficit in Drosophila melanogaster exposed to photocatalytic products of Paraquat.

The Advanced Oxidative Processes have demonstrated potential for application in the degradation of organic pollutants, such as Paraquat (PQ) from water and wastewater, due to their low price, high efficiency, and non-toxic properties. In this study, we investigated whether the photodegradation of PQ with TiO2 nanotubes reduced its toxicity in Drosophila melanogaster. However, dietary ingestion of degradation products PQ for larvae resulted in a low axial ratio (pupal volume). In the adults, products of photodegradation of PQ exposure markedly diminished climbing ability in a time-dependent manner after 10 days of feeding. In addition, exposure of D. melanogaster to photodegradation of PQ reduced acetylcholinesterase and citrate synthase activities but improved oxidative stress, as evidenced by oxide nitric, protein carbonyl, and lactate production. These results suggest that the photodegradation of PQ with TiO2 nanotubes produced PQ fragments with higher toxicity than PQ, while the precise mechanism of its action needs further investigation.

Chemical characterization, in vivo safety profile and effects of the extract from unconventional food plant Acca sellowiana (O. BERG) Burret on endothelial cells under glucose overload.

"Guava" (Acca sellowiana) is an unconventional edible plant from Brazil. It is used in traditional medicine as an anti-diabetic; however, pharmacological studies on this plant are scarce. This study aimed to evaluate the chemical and safety profile of an aqueous A. sellowiana peel extract (ASPE) and its effects on endothelial EA.hy926 cells under glucose overload and in vivo (Artemia salina). An ethanolic extract from A. sellowiana peels (ASPEetOH) was also produced and characterized. Results showed that ASPE did not present in vivo toxicity, and it was found to contain high phenolic content and redox capacity. ASPE (50 µg/mL; 24 h) prevented oxidative stress and mitochondrial dysfunction, besides positively modulating Sirtuins 1 and 3, and prevented the increase of COX-2 and NF-kß expression levels in EA.hy926 cells under glucose overload. Chromatographic fractionation, metabolite profiling, spectroscopic and bioinformatics analyses revealed the presence of phenolic acids, flavan-3-ols, flavonols, flavones, flavanones, and anthocyanidins, displaying a diversity of compounds in the crude and fractionated ASPEetOH. This study provided evidence on the safety profile, chemical composition, and pharmacological activities of A. sellowiana.

What's in drugs freely used by Brazilian truck drivers - "Rebites"? Determination of target and nontarget compounds by high-resolution mass spectrometry and nuclear magnetic resonance.

Highways, the lifeline of the Brazilian economy, transport approximately 75% of the country's economic activity, highlighting its importance. However, professional drivers, accustomed to long daily journeys, make use of tablets widely available in Gas Station, which are known as "Rebites," which could contain a mixture of legal and illegal compounds. Thus, this study aims at the chemical characterization of these through different analytical methods. Initially, we performed a comprehensive screening of compounds present in seven samples collected across the country using high-resolution mass spectrometry (HRMS). The findings revealed caffeine as the main compound, alongside theophylline, lidocaine, and clobenzorex, among others. In the next step, we employ quantitative nuclear magnetic resonance (qNMR) to quantify the caffeine content in the tablets. The results indicated a caffeine concentration ranging between 14% and 31% (m/m), which may imply a daily overdose of this compound from around four tablets. In summary, this investigation provides a chemical characterization of real samples of "Rebites" freely obtained along Brazilian highways. Caffeine emerged as the predominant active compound, with its concentration determined by qNMR analysis. The notable presence of caffeine, combined with other stimulants, depressants, and hallucinogens, underscores the need for strict quality control measures regarding "Rebites" to safeguard public health.

Chemical characterization of Callingcard Vine (Entada polystachya (L.) DC. var. polystachya) aqueous seed extract and evaluation of its cytotoxic, genotoxic and mutagenic properties.

Callingcard Vine (Entada polystachya (L.) DC. var. polystachya - Fabaceae) is a common plant in coastal thickets from western Mexico through Central America to Colombia and Brazil, especially in Amazon biome. It has been popularly used as a urinary burning reliever and diuretic. However, the plant chemical constituents are poorly understood and Entada spp. genotoxic potential have not been previously investigated. In the present study we determined the chemical composition of the aqueous E. polystachya crude seed extract (EPCSE) and evaluated the cytotoxic, genotoxic and mutagenic properties of EPCSE in Salmonella typhimurium and Chinese hamster fibroblast (V79) cells. Cytotoxic activity was also evaluated in tumor cell lines (HT29, MCF7 and U87) and non-malignant cells (MRC5). The chemical analysis by High Resolution Mass Spectrometry (HRMS) of EPCSE indicated the presence of saponin and chalcone. The results of the MTT and clonal survival assays suggest that EPCSE is cytotoxic to V79 cells. Survival analysis showed higher IC50 in non-tumor compared with tumor cell lines. EPCSE showed induction of DNA strand breaks as revealed by the alkaline comet assay and micronucleus test. Using the modified comet assay, it was possible to detect the induction of oxidative DNA base damage by EPCSE in V79 cells. Consistently, the extract induced increase lipid peroxidation (TBARS), superoxide dismutase (SOD) and catalase (CAT) activities in V79 cells. In addition, EPCSE induced mutations in S. typhimurium TA98 and TA100 strains, confirming a mutagenic potential. Taken together, our results suggest that EPCSE is cytotoxic and genotoxic to V79 cells and mutagenic to S. typhimurium. These properties can be related to the pro-oxidant ability of the extract and induction of DNA lesions. Additionally, EPCSE could inhibit the growth of tumor cells, especially human colorectal adenocarcinoma (HT29) cell line, and can constitute a possible source of antitumor natural agents.

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones.

An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110-120 °C, the reaction preferentially afforded 1H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, whereas using Yb(OTf)3 in MeCN reflux, 2H-pyrazolo[3,4-d]pyridazin-7(6H)-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.

Pesticides analysis in alternative biological matrices.

This review aims to bring together the works on pesticide analysis in alternative biological matrices, such as hair, breast milk, meconium, and placenta. Much is known about the harmful effects of the use and indirect consumption of pesticides; however, the assessment of long-term contamination is still unclear. In this sense, the use of hair as an alternative biological matrix has some advantages, such as segmentation, which makes it possible to assess the presence of xenobiotics to which individuals have been exposed over the years, and possibly relate this exposure to symptoms or diseases that may affect them. Complementarily, the other matrices discussed are able to provide information about the exposure of mothers and newborn children, who may have been indistinctly exposed to pesticides while in the womb. Through the analysis of studies already performed, it can be observed that organochlorine pesticides (OCPs) are the most likely to be found within the biological matrices discussed here, due to the lipophilic characteristics of these compounds. For the other classes, biotransformation products are more easily detected.

Characterization of Brazilian floral honey produced in the states of Santa Catarina and São Paulo through ultraviolet-visible (UV-vis), near-infrared (NIR), and nuclear magnetic resonance (NMR) spectroscopy.

Honey is considered a complex matrix for presenting a range of secondary metabolites originating from the regional flora. It has been highlighted as a functional food consumed worldwide and frequently suffering from adulteration. Fraud methods have been sophisticated over the years, indicating the need of a continuous updating of the existing analysis methods. For this reason, analytical techniques applied to honey have been expanded, allowing the detection of fraud and the determination of geographic and botanical origin, to guarantee the authenticity of the product. In this sense, this study aimed to characterize floral honey samples in 2019-2020 and 2020-2021 harvests in the states of Santa Catarina (SC, southern Brazil - n = 73) and São Paulo (SP, southeastern Brazil - n = 59), through UV-vis, NIR, and NMR spectroscopies. The total reduced capacity showed a wide variation (0.76-12.8 mg GAE.g-1) among the SC and SP samples. Spectroscopic analyses through UV-vis and NMR with the application of PCA proved effective for discriminating honey samples according to their geographical origin. The honey UV-vis spectral profiles allowed to detect wavelengths that can be associated with honey adulteration, however further studies are needed to establish the accuracy of detection regarding fraud. In summary, a set of analytical protocols is presented to determine the geographical origin of floral honey, even when originated from regions with great biodiversity such as Brazil.

Characterization of Planktochlorella nurekis Extracts and Virucidal Activity against a Coronavirus Model, the Murine Coronavirus 3.

Certain members of the Coronaviridae family have emerged as zoonotic agents and have recently caused severe respiratory diseases in humans and animals, such as SARS, MERS, and, more recently, COVID-19. Antivirals (drugs and antiseptics) capable of controlling viruses at the site of infection are scarce. Microalgae from the Chlorellaceae family are sources of bioactive compounds with antioxidant, antiviral, and antitumor activity. In the present study, we aimed to evaluate various extracts from Planktochlorella nurekis in vitro against murine coronavirus-3 (MHV-3), which is an essential human coronavirus surrogate for laboratory assays. Methanol, hexane, and dichloromethane extracts of P. nurekis were tested in cells infected with MHV-3, and characterized by UV-vis spectrophotometry, nuclear magnetic resonance (NMR) spectroscopy, ultraperformance liquid chromatography-mass spectrometry (UPLC-MS), and the application of chemometrics through principal component analysis (PCA). All the extracts were highly efficient against MHV-3 (more than a 6 Log unit reduction), regardless of the solvent used or the concentration of the extract, but the dichloromethane extract was the most effective. Chemical characterization by spectrophotometry and NMR, with the aid of statistical analysis, showed that polyphenols, carbohydrates, and isoprene derivatives, such as terpenes and carotenoids have a more significant impact on the virucidal potential. Compounds identified by UPLC-MS were mainly lipids and only found in the dichloromethane extract. These results open new biotechnological possibilities to explore the biomass of P. nurekis; it is a natural extract and shows low cytotoxicity and an excellent antiviral effect, with low production costs, highlighting a promising potential for development and implementation of therapies against coronaviruses, such as SARS-CoV-2.

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones.

The broad application of 1H-indazoles has prompted the development of several approaches for the synthesis of such compounds, including metal-free, palladium-, or copper-promoted intramolecular N-arylation of in situ-generated or isolated o-haloarylhydrazones. Such methods mainly start from o-bromo derivatives due to the better yield observed when compared to those obtained from o-chloroarylhydrazones. However, the o-chloroarylaldehydes and o-chloroarylketones used to prepare the arylhydrazones are more commercially available and less expensive than brominated analogs. Seeking to cover a lack in the literature, this work reports a convenient protocol for the synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of o-chlorinated arylhydrazones. Therefore, a series of seven N-phenyl derivatives and a series of six novel N-thiazolyl derivatives was obtained in 10-70% and 12-35% yield, respectively, after stirring the o-chlorinated arylhydrazones, CuI, KOH, and 1,10-phenantroline for 12-48 hours in DMF at 120 °C. The products were isolated by column chromatography on silica gel. All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the first reported synthesis of pharmacologically interesting N-thiazolyl derivatives.

Dual effect of the herbal matcha green tea (Camellia sinensis L. kuntze) supplement in EA.hy926 endothelial cells and Artemia salina.

ETHNOPHARMACOLOGICAL RELEVANCE: Matcha green tea (Camellia sinensis) based-supplements have been widely used since they present a greater content of phenolic compounds than traditional green tea, which is popularly used in the treatment of diabetes. However, there are few studies on the effectiveness and safety of matcha supplements. AIM OF THE STUDY: This work aimed to evaluate the efficacy and safety of this supplement in endothelial cells (EA.hy926) in the hyperglycemic model and in vivo Artemia salina. MATERIALS AND METHODS: To assess the effect of Matcha herbal supplement (MHS), EA. hy926 endothelial cells were treated with 20 µg/mL of MHS for 24 h, in a hyperglycemic medium with 35 mM glucose. After treatment, cells were trypsinized and centrifuged at 4 °C and 47×g for 5 min. The pellet was used to determine the reaction products to thiobarbituric acid and the levels of nitric oxide. Electron transport chain activity and ATP levels were also evaluated. Intracellular pH, apoptosis, and mitochondrial membrane depolarization were evaluated by flow cytometry. MHS chemical characterization was performed by HPLC-UV and total phenolic content analysis. The evaluation of the antioxidant capacity of MHS was performed by 2,2-diphenyl-1-picrylhydrazyl radical scavenger assay. To determine the in vivo acute toxicity of MHS, an A. salina assay was conducted, using 0,2 mL of different concentrations of MHS (10, 50, 100, 250, 500, 750 and 1000 µg/mL). The LD50 values were obtained by interpolation of 50% (y = 50) of the dead individuals in the trend curves. RESULTS: Our data showed that MHS was able to avoid oxidative and nitrosative stress induced by hyperglycemia, demonstrating important antioxidant activity. However, it was observed that MHS reduced up to 90% the activity of the four-electron transport complexes, reducing the ATP production of the endothelial cells. In the toxicity assay performed in Artemia salina, MHS showed mild toxicity (LD50 = 0,4 mg/mL). The major compounds found in MHS were epigallocatechin gallate, epicatechin, rutin, kaempferol, and quercetin. CONCLUSIONS: This data draws attention to the fact that supplements with high content of phenolic compounds, capable of avoiding oxidative and nitrosative stress can have a dual effect and, simultaneously to antioxidant activity, can induce toxicity in different cell types.

Four almost unexplored species of Brazilian Connarus (Connaraceae): Chemical composition by ESI-QTof-MS/MS-GNPS and a pharmacologic potential.

INTRODUCTION: Species of Connaraceae are globally used in traditional medicines. However, several of these have not been studied regarding their chemical composition, and some are even at risk of extinction without proper studies. Therefore, the chemical composition and pharmacological potential of Connarus blanchetii Planch., Connarus nodosus Baker, Connarus regnellii G. Schellenb., and Connarus suberosus Planch., which were previously unknown, were analyzed. OBJECTIVE: This work aims to investigate the pharmacological potential of these four Connarus species. The chemical composition of different extracts was determined by high-resolution mass spectrometry (HRMS), with subsequent analysis by the GNPS platform and competitive fragmentation modeling (CFM). MATERIALS AND METHODS: Leaf extracts (C. blanchetii, C. nodosus, C. regnellii, and C. suberosus) and bark extracts (C. regnellii and C. suberosus) were obtained by decoction, infusion, and maceration. LC/HRMS data were submitted to the GNPS platform and evaluated using CFM in order to confirm the structures. RESULTS: The HRMS-GNPS/CFM analysis indicated the presence of 23 compounds that were mainly identified as phenolic derivatives from quercetin and myricetin, of which 21 are unedited in the Connarus genus. Thus, from the analyses performed, we can identify different compounds with pharmacological potential, as well as the most suitable forms of extraction. CONCLUSION: Using HRMS-GNPS/CFM, 21 unpublished compounds were identified in the studied species. Therefore, our combination of data analysis techniques can be used to determine their chemical composition.

Synthesis and Antiprotozoal Profile of 3,4,5-Trisubstituted Isoxazoles.

Invited for this month's cover picture is the group of Prof. Fernanda Andreia Rosa at the State University of Maringá (Brazil). The cover picture shows the contribution of the SINTHET research group to the synthesis and discovery of new antiprotozoal compounds. The synthetic methodology allowed the construction of 60 new isoxazole derivatives with structural variations on the 3-, 4-, and 5-positions. The authors acknowledge Ms. Jeniffer do Nascimento Ascencio Camargo and Ms. Julia Caroline Manzano Willig for the Cover picture creation. Read the full text of their Full Paper at 10.1002/open.202100141.

Saccharomyces cerevisiae DNA repair pathways involved in repair of lesions induced by mixed ternary mononuclear Cu(II) complexes based on valproic acid with 1,10-phenanthroline or 2,2'- bipyridine ligands.

The sodium valproate has been largely used as an anti-epilepsy drug and, recently, as a putative drug in cancer therapy. However, the treatment with sodium valproate has some adverse effects. In this sense, more effective and secure complexes than sodium valproate should be explored in searching for new active drugs. This study aims to evaluate the cytotoxicity of sodium valproate, mixed ternary mononuclear Cu(II) complexes based on valproic acid (VA) with 1,10-phenanthroline (Phen) or 2,2'- bipyridine (Bipy) ligands - [Cu2(Valp)4], [Cu(Valp)2Phen] and [Cu(Valp)2Bipy] - in yeast Saccharomyces cerevisiae, proficient or deficient in different repair pathways, such as base excision repair (BER), nucleotide excision repair (NER), translesion synthesis (TLS), DNA postreplication repair (PRR), homologous recombination (HR) and non-homologous end-joining (NHEJ). The results indicated that the Cu(II) complexes have higher cytotoxicity than sodium valproate in the following order: [Cu(Valp)2Phen] > [Cu(Valp)2Bipy] > [Cu2(Valp)4] > sodium valproate. The treatment with Cu(II) complexes and sodium valproate induced mutations in S. cerevisiae. The data indicated that yeast strains deficient in BER (Ogg1p), NER (complex Rad1p-Rad10p) or TLS (Rev1p, Rev3p and Rad30p) proteins are associated with increased sensitivity to sodium valproate. The BER mutants (ogg1Δ, apn1Δ, rad27Δ, ntg1Δ and ntg2Δ) showed increased sensitivity to Cu(II) complexes. DNA damage induced by the complexes requires proteins from NER (Rad1p and Rad10p), TLS (Rev1p, Rev3p and Rad30p), PRR (Rad6 and Rad18p) and HR (Rad52p and Rad50p) for efficient repair. Therefore, Cu(II) complexes display enhanced cytotoxicity when compared to the sodium valproate and induce distinct DNA lesions, indicating a potential application as cytotoxic agents.

Synthesis and Antiprotozoal Profile of 3,4,5-Trisubstituted Isoxazoles.

A series of 60 4-aminomethyl 5-aryl-3-substituted isoxazoles were synthesized by an efficient method and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi, protozoa that cause the neglected tropical diseases leishmaniasis and Chagas disease, respectively. Thirteen compounds exhibited a selective index greater than 10. The series of 3-N-acylhydrazone isoxazole derivatives bearing the bithiophene core exhibited the best antiparasitic effects.

Cytotoxic Effects of Diclofenac and Ibuprofen Zinc (II)-Nicotinamide Ternary Complexes in Breast Cancer Cell Lines

Abstract Breast cancer is one of the leading types of cancer worldwide, and the search for new treatment options are crucial. Nonsteroidal anti-inflammatory drugs (NSAIDs) -specially ibuprofen and diclofenac-, have shown antitumoral effect against several types of cancer. The synthesis of organometallic compounds has shown significant improvements in pharmacological properties and efficacy of organic molecules. Two zinc II ternary complexes containing the NSAIDs diclofenac and ibuprofen and nicotinamide neutral linker (Nic) were obtained by the two-step solvent metalligand complexation method. The compounds Zn2(Diclof)4(Nic)2 (complex 1) and Zn2(Ibup)4(Nic)2 (complex 2) were tested in breast cancer cell lines (4T1, MCF-7 and MDA-MB-231) to evaluate their cytotoxicity, comparing to ibuprofen and diclofenac as controls. We found that both complex 1 and 2 exerted more than 60% reduction in 4T1 viability at 250µM, and complex 2 decreased cell viability at 250 µM and 137.5 µM in MCF-7 (34.35% and 26.42% reduction, respectively) and in MDA-MB-231 (57.2% and 22.88% reduction, respectively), all compared to controls. Complex 1 was selective only in MCF-7, and complex 2 was selective in both MCF-7 and MDA-MB-231. In summary, our data showed that the cytotoxic effect of complex 1 and 2 is increased comparing to their original NSAID in different breast cancer cell lines, highlighting their potential anti-tumoral activity.

The Insecticidal Activity of Rhinella schneideri (Werner, 1894) Paratoid Secretion in Nauphoeta cinerea Cocroaches.

Rhinella schneideri is a common toad found in South America, whose paratoid toxic secretion has never been explored as an insecticide. In order to evaluate its insecticidal potential, Nauphoeta cinerea cockroaches were used as an experimental model in biochemical, physiological and behavioral procedures. Lethality assays with Rhinella schneideri paratoid secretion (RSPS) determined the LD50 value after 24 h (58.07µg/g) and 48 h exposure (44.07 µg/g) (R2 = 0.882 and 0.954, respectively). Acetylcholinesterase activity (AChE) after RSPS at its highest dose promoted an enzyme inhibition of 40%, a similar effect observed with neostigmine administration (p < 0.001, n= 5). Insect locomotion recordings revealed that RSPS decreased the distance traveled by up to 37% with a concomitant 85% increase in immobile episodes (p < 0.001, n = 36). RSPS added to in vivo cockroach semi-isolated heart preparation promoted an irreversible and dose dependent decrease in heart rate, showing a complete failure after 30 min recording (p < 0.001, n ≥ 6). In addition, RSPS into nerve-muscle preparations induced a dose-dependent neuromuscular blockade, reaching a total blockage at 70 min at the highest dose applied (p < 0.001, n ≥ 6). The effect of RSPS on spontaneous sensorial action potentials was characterized by an increase in the number of spikes 61% (p < 0.01). Meanwhile, there was 42% decrease in the mean area of those potentials (p < 0.05, n ≥ 6). The results obtained here highlight the potential insecticidal relevance of RSPS and its potential biotechnological application.

Antiparasitic Behavior of Trifluoromethylated Pyrazole 2-Amino-1,3,4-thiadiazole Hybrids and Their Analogues: Synthesis and Structure-Activity Relationship.

A series of trifluoromethylated pyrazole thiosemicarbazone, trifluromethylated pyrazole isothiosemicarbazone, and trifluoromethylated pyrazole 2-amino-1,3,4-thiadiazole hybrids were synthesized and evaluated in vitro against the promastigote form of Leishmania amazonensis and the epimastigote form of Trypanosoma cruzi, the pathogens causing the neglected tropical diseases leishmaniasis and Chagas disease, respectively. The results show the potential of these compounds regarding their antiparasitic properties. Studies on the structure-activity relationship demonstrated that compounds containing a bulky group at the para position of the phenyl ring attached to the 5-position of the pyrazole core had better antiparasitic effects. Among the substituents attached at the 3-position of the pyrazole ring, the insertion of the 2-amino-1,3,4-thiadiazole nucleus led to the most potent compounds compared to the thiosemicarbazone derivative.

Exploring the chemical profile of designer drugs by ESI(+) and PSI(+) mass spectrometry-An approach on the fragmentation mechanisms and chemometric analysis.

The consumption of design drugs, frequently known as new psychoactive substances (NPS), has increased considerably worldwide, becoming a severe issue for the responsible governmental agencies. These illicit substances can be defined as synthetic compounds produced in clandestine laboratories in order to act as analogs of schedule drugs mimetizing its chemical structure and improving its pharmacological effects while hampering the control and making regulation more complicated. In this way, the development of new methodologies for chemical analysis of NPS drugs is indispensable to determine a novel class of drugs arising from the underground market. Therefore, this work shows the use of high-resolution mass spectrometry Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) applying different ionization sources such as paper spray ionization (PSI) and electrospray ionization (ESI) in the evaluation of miscellaneous of seized drugs samples as blotter paper (n = 79) and tablet (n = 100). Also, an elucidative analysis was performed by ESI(+)MS/MS experiments, and fragmentation mechanisms were proposed to confirm the chemical structure of compounds identified. Besides, the results of ESI(+) and PSI(+)-FT-ICR MS were compared with those of GC-MS, revealing that ESI(+)MS showed greater detection efficiency among the methodologies employed in this study. Moreover, this study stands out as a guide for the chemical analysis of NPS drugs, highlighting the differences between the techniques of ESI(+)-FT-ICR MS, PSI(+)-FT-ICR MS, and GC-MS.

Chemical Characterization of Lavandula dentata Essential Oil Cultivated in Chile and Its Antibiofilm Effect against Candida albicans.

Candida albicans is the most common human fungal pathogen, and with the increase in resistance rates worldwide, it is necessary to search for new pharmacological alternatives. Lavandula dentata L. essential oil is recognized as having antimicrobial properties. However, its effect against fungal biofilms has been poorly described. C. albicans-related infections involve the development of biofilms, which are highly resistant to conventional antifungals. In this work, we evaluated the antibiofilm effect of L. dentata L. essential oil against C. albicans. First, we characterized the essential oil by gas chromatography-mass spectrometry. The antifungal effect on C. albicans reference strains was evaluated by a disk diffusion assay and the minimal inhibitory concentration was obtained through a microdilution assay. The effect of the essential oil on the adhesion ability of C. albicans was determined through a crystal violet assay, and morphogenesis inhibition was assessed by light microscopy. The effect of the essential oil on the microarchitecture of biofilms was evaluated through scanning electron microscopy. Finally, the antibiofilm effect was evaluated through an adapted biofilm scratch assay and XTT viability assay. The main constituent of the essential oil was the monoterpenoid eucalyptol (60%). The essential oil presented minimal inhibitory concentrations of 156 and 130 µg/mL against two strains assayed. This minimal inhibitory concentration inhibited adhesion, morphogenesis, biofilm formation, altered microarchitecture, and decreased the viability of established biofilms formed on abiotic surfaces for both strains assayed. This study demonstrates that the essential oil from L. dentata could be a promising treatment against C. albicans biofilms.

Selection of low nitrogen demand yeast strains and their impact on the physicochemical and volatile composition of mead.

Mead is an ancient alcoholic beverage produced through the fermentation of a diluted solution of honey. Due to the peculiar and varied composition of honey, mead production faces several problems, such as slow or stuck fermentations mainly due to the low nitrogen concentration, lack of uniformity of the final product and the production of unpleasant aromas. In this context, this work aimed to select low nitrogen-demand yeast strains and evaluate their potential for the production of mead. Therefore, among 21 commercial wine yeast strains, 5 were selected based on their fermentative behavior at low assimilable nitrogen concentrations. The selected strains were further evaluated for their contributions in meads produced with limited nitrogen availability, and the results showed significant differences on some physicochemical parameters like biomass production, residual sugars, glycerol concentration, and fermentative rate. Moreover, meads obtained with selected strains differed in the concentration of several volatile compounds. The volatile compounds concentration and the principal component analysis based on odor activity values allowed separating strains into three groups. In general, S. cerevisiae var bayanus strains (QA23, Spark, and AWRI-R2) were the largest producers of aromatic compounds, particularly those with floral and fruity descriptors. The selection of yeast strains with low nitrogen-demand and different volatile compounds production can be explored by mead makers to limit fermentation problems and obtain characteristic products.