Bioactives of Melipona rufiventris Propolis: Exploring its Antimicrobial, Anti-Inflammatory, and Antioxidant Activities.

This study explores the potential of propolis, a resinous substance produced by bees, from Melipona rufiventris species. With its composition encompassing resin, wax, pollen, and soil, propolis holds historical significance in traditional medicine within tropical regions. This research is driven by the scarcity of information surrounding M. rufiventris propolis, prompting an investigation into its chemical constituents, in vivo toxicity, and antimicrobial, antioxidant, and anti-inflammatory properties. This exploration could potentially uncover novel applications for this natural product, bolstering both meliponiculture practices and the preservation of native bee populations. The propolis was sampled in Cabo Verde-MG and underwent ethanolic extraction to yield an extract (EEP) for analysis. Chemical assessments (Folin-Ciocalteau, and UHPLC-HRMS) revealed the presence of polyphenols, including flavonoids. The EEP demonstrated higher antimicrobial activity against Gram-positive bacteria and exhibited efficacy against multiresistant strains isolated from complex wounds. Synergistic interactions with commercial antibiotics were also observed. Furthermore, anti-inflammatory evaluations showcased the EEP's potential in reducing NF-kB activation and TNF-α release at non-toxic concentrations. Despite these promising biological activities, the EEP exhibited no antiproliferative effects and demonstrated safety in both the MTS assay and the G. mellonella model. Collectively, these findings highlight the M. rufiventris propolis extract as a valuable reservoir of bioactive compounds with multifaceted potential.

Itraconazole and neutrophil interactions in the immune-inflammatory response of paracoccidioidomycosis using a murine air pouch infection model.

Paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis (Pb), is a severe mycosis, prevalent in tropical countries. The presence of polymorphonuclear neutrophils (PMN) in lesions is conspicuous, indicating their central role in innate immunity through the direct killing of Pb and the production of cytokines that activate acquired immunity in the presence of itraconazole (Itra). The toxicity and direct antifungal activity of Itra on Pb in splenocyte co-cultures were evaluated in vitro. Itra showed no toxic effect but marked antifungal activity against Pb. Purified PMN were obtained by the subcutaneous (SC) injection of Pb into mice. Results showed the effect of Itra on the size of the air pouch produced, the cellular population that migrated to the infection site, protein, and mitochondrial metabolism patterns, production of ROS an NO, and the number of cytokines synthesized. Lower doses (3 and 10 mg/kg) of Itra did not affect the cellular profile but led to a lower influx of viable more active PMN, and increased production of ROS and proteins. At a dose of 50 mg/kg the PMN profile remained unchanged along with all other parameters analyzed remained unaltered. Decreases in most cytokine levels were inversely proportional to the Itra concentration. Lower Itra concentrations may elicit activation of the immune response because the combined effects of therapy and immune response are needed, while the higher dose does not require it. Itra also promotes the activation of the cytokines which elicit PMN activation and consequently the resolution of Pb18 infection in the air pouch.

Dynamic gastrointestinal digestion/intestinal permeability of encapsulated and nonencapsulated Brazilian red propolis: Active compounds stability and bioactivity.

The objectives were to investigate the effect of dynamic gastrointestinal digestion/Caco-2 cell transport on active compounds stability and antioxidant/anti-inflammatory activities of the ethanolic extract of Brazilian red propolis (EEBRP), whether encapsulated or not; and the in vivo acute toxicity of the EEBRP after digestion. Eight isoflavonoids, one flavanone, and one chalcone were identified by HPLC-ESI-QTOF-MS, and quantified by HPLC-PDA. Bioaccessibility was higher for the encapsulated EEBRP (21.4%-57.6%) than for the nonencapsulated (19.3%-30.2%). Conversely, the Caco-2 cell transport was higher for the nonencapsulated EEBRP. Similarly, the nonencapsulated EEBRP showed higher ability to scavenge reactive oxygen species, which was especially attributed to calycosin, and to decrease NF-κB activation, and the levels of TNF-α and CXCL2/MIP-2 after Caco-2 cell transport. Hence, there is an indication that EEBRP is a promising alternative dietary source of bioavailable isoflavonoids. Further studies on encapsulation should be encouraged to improve bioactivity, and expand its food applications.

A Systematic Review of the Potential Effects of Propolis Extracts on Experimentally-induced Diabetes.

Oxidative stress (OS) is involved in the development of diabetes mellitus (DM) and its complications. Thus, OS reduction may be an important strategy for DM therapy. Propolis is bee resins with high antioxidant activity and is used in the treatment of different diseases, including DM. Therefore, in this systematic review, we evaluated the impact of propolis administration in diabetic animals. We used the PRISMA strategy to collect preclinical studies published in English up to November 2021 in three databases (PubMed/Medline, Scopus, and Web of Science). We used the SYRCLE tool to analyze the risk of methodological bias. Our primary search returned 198 studies, of which 14 were considered eligible to be included in this review. The administration of propolis induced a hypoglycemic effect in the treated animals, which is probably due to the reduction of OS. The animals showed restoration of endogenous antioxidant defenses and reduced levels of markers for OS. The administration of propolis resulted in improvement in the lipid profile of treated animals. Our risk of bias assessment showed a methodological quality score of less than 30% due to a lack of randomization, blinding, and proper allocation of animals. Heterogeneity in treatments, lack of results, and use of non-standard extracts are limitations in our data analysis. Despite these limitations, propolis induced a significant hypoglycemic effect in diabetic animals when compared to untreated controls. This effect was associated with a reduction in OS, a process mediated by ROS neutralization and restoration of endogenous antioxidant defenses.

Simulated gastrointestinal digestion/Caco-2 cell transport: Effects on biological activities and toxicity of a Brazilian propolis.

The objective was to assess the effect of gastrointestinal digestion/Caco-2 cell transport on biological activities and toxicity of the ethanolic extract of organic propolis from southern Brazil (EEOP1). As principal results, the EEOP1 deactivated the ROO•, HOCl and O2•- reactive oxygen species, attenuated NF-κB transcription factor activation, and decreased the release of TNF-α and IL-6 in macrophages after Caco-2 cell transport, while CXCL2/MIP-2 release was reduced after gastrointestinal digestion. Furthermore, the phytochemical profile monitored by HPLC-ESI-QTOF-MS changed, especially for lignans, lignan-precursors and phenolic acids. Conversely, the antimicrobial activity was observed only in the non-digested EEOP1. The EEOP1 lethal dose to kill 50 % of the Galleria mellonella larvae was 1.1 g/kg, and its digested fraction had no toxic effect. Hence, there is indication that some phytochemicals present in the EEOP1 are resistant to the gastrointestinal tract and maintain their biological activities, as expected for a functional food ingredient.

Plant genetic diversity by DNA barcoding to investigate propolis origin.

Identify the botanical origins of a certain type of propolis may be challenging and time demanding, since it involves bee's behavior observation, plant resins collection and chemical analysis. Thus, this study aimed to determine the plant genetic materials in propolis from southern Brazil using the DNA barcoding to investigate their botanical origins, as well as to compare it with the phytochemical composition determined by ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) and with the pollinic profile. As principal results, non-native Populus carolinensis Moench (Salicaceae) was almost the only DNA source in some propolis samples, which coincided with the presence of flavonoids typical from poplar exudates. Conversely, other propolis samples had DNA material coming mainly from native plant species, most of them characterized to the species level, although no specific chemical markers from those plants could be identified by UHPLC-HRMS. However, pollen from several plants identified by the DNA barcoding were extracted from some propolis samples. Despite the identification of typical diterpenes, DNA material from Araucaria angustifolia (Bertol.) Kuntze (Araucariaceae), which have been indicated as a major resin source for propolis from preservation areas in southern Brazil, was found in very small abundancies, likely because bees do not drag tissue material containing DNA when collecting resin from this native species. In conclusion, DNA barcoding analysis successfully provided information about the provenance of propolis, although, depending on the plant resin sources, this information is likely to come from pollen.

Lignans as new chemical markers of a certified Brazilian organic propolis.

Commercially certified organic propolis produced in areas of environmental conservation and reforestation forests of Southern Brazil are generally poor in flavonoids, although one of its variants - Brazilian certified organic propolis 1 (OP1) - has shown strong antioxidant activity. The objective was to identify active compounds from OP1 related to its strong antioxidant activity. OP1 ethanolic extracts were subjected to liquid-liquid fractionation, and the fractions presenting the strongest antioxidant activity were combined and purified into subfractions. Compounds isolated from the most active subfractions had their structure elucidated by Nuclear Magnetic Resonance (NMR). As a result, five lignans and two lignan-precursors were isolated, and four of them are herein reported for the very first time in propolis. Hence, these compounds may be used as chemical markers for product standardization and authentication purposes, since OP1 is only produced by honeybees in native forests and its botanical origins remain unknown.

An insight into the botanical origins of propolis from permanent preservation and reforestation areas of southern Brazil.

Brown propolis from permanent preservation and reforestation areas of southern Brazil have attracted international commercial interest and have a unique composition, although little is known about their botanical origins, which are the plant resins used by bee foragers to produce propolis. Hence, the volatile profiles of organic and non-organic brown propolis and resins of suspected botanical origins-Araucaria angustifolia, Pinus elliott and Pinus taeda-were determined using static headspace gas chromatography coupled to mass spectrometry (SHS-GCMS) and compared. Nighty nine volatiles were tentatively identified, and monoterpenes and sesquiterpenes were the most abundant classes. Principal component analysis (PCA) showed similarity between organic propolis and A. angustifolia volatile profiles (p < 0.05). Hierarchical clustering analysis showed singularities among propolis, even between propolis produced 1 km away from each other. Heatmaps were used to identify peaks present in similar relative intensities in both propolis and conifer resins. Hence, the approach using volatile profiles shed light to propolis botanical origins, which is important for authentication and traceability purposes.

Brazilian Red Propolis shows antifungal and immunomodulatory activities against Paracoccidioides brasiliensis.

ETHNOPHARMACOLOGICAL RELEVANCE: Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in South America and especially in Brazil with severe clinical consequences that need broadened therapeutic options. Propolis is a natural resin from bees used in folk medicine for centuries with the first report in the ancient history of Egypt by Eberly papyrus, in Middle-Ages used to wash the newborn's umbilical cord and World War II as antiseptic or antibiotics. Nowadays it is a natural product worldwide consumed as food and traditionally used for oral and systemic diseases as an anti-inflammatory, antimicrobial, antifungal, and other diseases. Brazilian red propolis (BRP) is a new type of propolis with a distinguished chemical profile and biological activities from propolis (green) with pharmacological properties such as antimicrobial, anti-inflammatory, antioxidant, and others. AIM OF STUDY: Thus, the main purpose of this study was to investigate the direct in vitro and ex vivo effect of BRP on Paracoccidioides brasiliensis. MATERIAL AND METHODS: Antifungal activity of different concentrations of BRP on a virulent P. brasiliensis isolate (Pb18) was evaluated using the microdilution technique. Also, mice splenic cells co-cultured with Pb18 were treated with BRP at different times and concentrations (only Pb18 = negative control). Mice were inoculated with Pb18 and treated with different concentrations of BRP (50-500 mg/mL) in a subcutaneous air pouch. In this later experimental model, macroscopic characteristics of the air pouch were evaluated, and cellular exudate was collected and analyzed for cellular composition, mitochondrial activity, total protein reactive oxygen specimens (ROS), and nitric oxide production, as well as the number of viable fungal cells. RESULTS: The in vitro experiments showed remarkable direct antifungal activity of BRP, mainly with the highest concentration employed (500 mg/mL), reducing the number of viable cells to 10% of the original inoculum after 72 h incubation. The splenocytes co-cultivation assays showed that BRP had no cytotoxic effect on these cells, on the contrary, exerted a stimulatory effect. This stimulation was also observed on the PMNs at the air pouch, as verified by production of ROS and total proteins and mitochondrial activity. This activation resulted in enhanced fungicidal activity, mainly with the 500 mg/mL concentration of BRP. An anti-inflammatory effect was also detected, as verified by the smaller volume of the BRP-treated air pouch as well as by an earlier shift from neutrophils to mononuclear cells present in the infection site. CONCLUSION: Our results strongly suggest, for the first time in the literature, that Brazilian Red propolis has four protective mechanisms in experimental paracoccidioidomycosis: activating neutrophils, exerting a direct antifungal effect, preventing fungal dissemination, and controlling excessive inflammation process.

Active Antioxidant Phenolics from Brazilian Red Propolis: An Optimization Study for Their Recovery and Identification by LC-ESI-QTOF-MS/MS.

Brazilian red propolis (BRP) is a natural product widely known for its phenolic composition and strong antioxidant properties. In this study, we used the Box-Behnken Design (BBD) with Surface Response Methodology to optimize the extraction conditions for total phenolic content (TPC) and Trolox equivalent antioxidant capacity(TEAC) of bioactive phenolics from BRP. The extraction time, ethanol/water concentration and temperature, were tested. All variables had significant effects (p ≤ 0.05), with a desirability coefficient of 0.88. Under optimized conditions (90% ethanol at 80 °C for 30 min), the BRP extract showed a TPC of 129.00 ± 2.16 mg GAE/g and a TEAC of 3471.76 ± 53.86 µmol TE/g. Moreover, FRAP and ORAC assays revealed that the optimized BRP extract had 1472.86 ± 72.37 µmol Fe2+/g and 4339.61 ± 114.65 µmol TE/gof dry weight, respectively. Thirty-two phenolic compounds were tentatively identified by LC-QTOF-ESI-MS/MS, of which thirteen were found for the first time in BRP, including four flavones, one flavanol, two flavanones, two chalcones, and four isoflavonoids. Thus, our results highlight the importance of BRP as a source of a wide variety of phenolic compounds with significant antioxidant properties.

A comprehensive characterization of polyphenols by LC-ESI-QTOF-MS from Melipona quadrifasciata anthidioides geopropolis and their antibacterial, antioxidant and antiproliferative effects.

The geopropolis is a unique type of propolis produced by some stingless bee species. This product is known in folk medicine for its pharmacological properties, mainly antimicrobial and antioxidant, but there are few scientific studies that prove these properties. The objective of this study was to evaluate the phenolic composition and the antimicrobial, antioxidant and antiproliferative activities of Melipona quadrifasciata geopropolis. The phenolic characterization of the geopropolis ethanolic extract was evaluated by LC-ESI-QTOF-MS. The antimicrobial activity was carried out against Gram-positive (including multiresistant microorganisms), negative and yeast. The synergistic effect was evaluated in association with Sulfamethoxazole + Trimethoprim. DPPH, ABTS, FRAP, ORAC and HPLC on-line were used to evaluate the antioxidant activity. Antiproliferative activity was assessed by the sulforhodamine B assay. Flavonoids and phenolic acids were identified in the extract, which showed promising antimicrobial activity, partially synergistic effect and antioxidant activity.

Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis.

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases.

The effect of seasons on Brazilian red propolis and its botanical source: chemical composition and antibacterial activity.

The aim of this study was to evaluate the effect of seasons on the chemical composition and antibacterial activity of Brazilian red propolis (BRP) and its plant source. BRP was collected from Maceio, Alagoas state, north-east of Brazil, during one year. Chemical composition was determined by physicochemical analyses and HPLC while antimicrobial activity was assessed against Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus and Actinomyces naeslundii by determining the minimal inhibitory and bactericidal concentrations (MIC and MBC, respectively). The comparative chemical profiles varied quantitatively according to the collection period. Formononetin was the most abundant compound in both propolis and resin, while isoliquiritigenin, (3S)-neovestitol, (3S)-vestitol are suggested to be responsible for antimicrobial activity of Brazilian red propolis. MIC varied from 15.6 to 125 µg/mL, whereas MBC varied from 31.2 to 500 µg/mL. Therefore, season in which propolis and its botanical source are collected indeed influences their chemical compositions, resulting in variations in their antibacterial activity.

Chemical Characterization and Antioxidant, Antimicrobial, and Anti-Inflammatory Activities of South Brazilian Organic Propolis.

South Brazilian organic propolis (OP), which has never been studied before, was assessed and its chemical composition, scavenging potential of reactive oxygen species, antimicrobial and anti-inflammatory activities are herein presented. Based on the chemical profile obtained using HPLC, OP was grouped into seven variants (OP1-OP7) and all of them exhibited high scavenging activity, mainly against superoxide and hypochlorous acid species. OP1, OP2, and OP3 had the smallest minimal inhibitory concentration (MIC) against Gram-positive bacteria Streptococcus mutans, Streptococcus oralis, and Streptococcus aureus (12.5-100 µg/mL). OP1, OP2, OP3, and OP4 were more effective against Pseudomonas aeruginosa (Gram-negative), with MIC values ranging from 100 to 200 µg/mL. OP6 showed anti-inflammatory activity by decreasing NF-kB activation and TNF-α release in RAW 264.7 macrophages, and expressing the NF-κB-luciferase reporter stable gene. Therefore, south Brazilian OP can be considered an excellent source of bioactive compounds with great potential of application in the pharmaceutical and food industry.

Prediction of pharmacokinetic and toxicological parameters of a 4-phenylcoumarin isolated from geopropolis: In silico and in vitro approaches.

In silico and in vitro methodologies have been used as important tools in the drug discovery process, including from natural sources. The aim of this study was to predict pharmacokinetic and toxicity (ADME/Tox) properties of a coumarin isolated from geopropolis using in silico and in vitro approaches. Cinnamoyloxy-mammeisin (CNM) isolated from Brazilian M. scutellaris geopropolis was evaluated for its pharmacokinetic parameters by in silico models (ACD/Percepta™ and MetaDrug™ software). Genotoxicity was assessed by in vitro DNA damage signaling PCR array. CNM did not pass all parameters of Lipinski's rule of five, with a predicted low oral bioavailability and high plasma protein binding, but with good predicted blood brain barrier penetration. CNM was predicted to show low affinity to cytochrome P450 family members. Furthermore, the predicted Ames test indicated potential mutagenicity of CNM. Also, the probability of toxicity for organs and tissues was classified as moderate and high for liver and kidney, and moderate and low for skin and eye irritation, respectively. The PCR array analysis showed that CNM significantly upregulated about 7% of all DNA damage-related genes. By exploring the biological function of these genes, it was found that the predicted CNM genotoxicity is likely to be mediated by apoptosis. The predicted ADME/Tox profile suggests that external use of CNM may be preferable to systemic exposure, while its genotoxicity was characterized by the upregulation of apoptosis-related genes after treatment. The combined use of in silico and in vitro approaches to evaluate these parameters generated useful hypotheses to guide further preclinical studies.

Cinnamoyloxy-mammeisin Isolated from Geopropolis Attenuates Inflammatory Process by Inhibiting Cytokine Production: Involvement of MAPK, AP-1, and NF-κB.

Chemical compounds belonging to the class of coumarins have promising anti-inflammatory potential. Cinnamoyloxy-mammeisin (CNM) is a 4-phenylcoumarin that can be isolated from Brazilian geopropolis. To our knowledge, its anti-inflammatory activity has never been studied. Therefore, the present study investigated the anti-inflammatory activity of CNM and elucidated its mechanism of action on isolated macrophages. Pretreatment with CNM reduced neutrophil migration into the peritoneal and joint cavity of mice. Likewise, CNM reduced the in vitro and in vivo release of TNF-α and CXCL2/MIP-2. Regarding the possible molecular mechanism of action, CNM reduced the phosphorylation of proteins ERK 1/2, JNK, p38 MAPK, and AP-1 (subunit c-jun) in PG-stimulated macrophages. Pretreatment with CNM also reduced NF-κB activation in RAW 264.7 macrophages stably expressing the NF-κB-luciferase reporter gene. On the other hand, it did not alter IκBα degradation or nuclear translocation of p65. Thus, the results of this study demonstrate promising anti-inflammatory activity of CNM and provide an explanation of its mechanism of action in macrophages via inhibition of MAPK signaling, AP-1, and NF-κB.

Antiproliferative Constituents of Geopropolis from the Bee Melipona scutellaris.

Fractionation of geopropolis from Melipona scutellaris, guided by antiproliferative activity against two colon cancer cell lines (COLO205 and KM12), led to the isolation of two new cinnamic acid esters, mammea-type coumarins 5,7-dihydroxy-6-(3-methyl-2-butenyl)-8-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-propyl-coumarin (1) and 5,7-dihydroxy-6-(4-cinnamoyl-3-methyl-1-oxobutyl)-4-phenylcoumarin (2), along with five known coumarins, mammeigin (3), hydroxymammeigin (4), mammeisin (5), cinnamoyloxy-mammeisin (6), and mammein (7), and the prenylated benzophenone ent-nemorosone (8). Among the isolated compounds, 5 and 7 showed the highest cell growth inhibition against COLO205 (GI50 9.7 and 10.7 µM, respectively) and KM12 (GI50 12.0 and 10.9 µM, respectively). The presence of these compounds suggests that plants of Clusiaceae family, especially the genera Kielmeyera and Clusia, are likely to be major sources of geopropolis produced by M. scutellaris.

Importance and Implications of the Production of Phenolic Secondary Metabolites by Endophytic Fungi: A Mini-Review.

In the natural products research, a valuable approach is the prospection of uncommon sources and unexplored habitat. Special attention has been given to endophytic fungi because of their ability to produce new and interesting secondary metabolites, which have several biological applications. The endophytes establish exclusive symbiotic relationships with plants and the metabolic interactions may support the synthesis of some similar valuables compounds. Among secondary metabolites, phenol-derived structures are responsible for several bioactivities such as antioxidant, cytotoxic, antimicrobial, among others. Phenolic compounds might be biosynthesized from the shikimate pathway. Although shikimic acid is a common precursor in plants, it is described as rare in microorganisms. To the best of our knowledge, this is the first review about phenolic compounds produced by endophytic fungi and a comparison has been made with those produced by the plant host. This review covers 124 phenolic secondary metabolites produced by endophytic fungi. Considering the data analyzed by us, only seven of such compounds were isolated from fungi and from their hosts. These observations claim for more attention to phenolic compounds produced by endophytic fungi with a view to understand the real importance of these compounds to endophytes survival.

Gastroprotective Effect of Geopropolis from Melipona scutellaris Is Dependent on Production of Nitric Oxide and Prostaglandin.

The aim of this study was to evaluate the gastroprotective activity of ethanolic extract of geopropolis (EEGP) from Melipona scutellaris and to investigate the possible mechanisms of action. The gastroprotective activity of the EEGP was evaluated using model ulcer induced by ethanol. To elucidate the possible mechanisms of action, we investigated the involvement of the nonprotein sulfhydryl (NP-SH) groups, nitric oxide and prostaglandins. In addition, the antisecretory activity of EEGP was also evaluated by pylorus ligated model. The EEGP orally administrated (300 mg/kg) reduced the ulcerative lesions induced by the ethanol (P < 0.05). Regarding the mechanism of action, the prior administration of nitric oxide and prostaglandins antagonists suppressed the activity of gastroprotective EEGP (P < 0.05). On the other hand the gastroprotective activity of EEGP was kept in the group pretreated with the antagonist of the NP-SH groups; furthermore the antisecretory activity was not significant (P > 0.05). These results support the alternative medicine use of geopropolis as gastroprotective and the activities observed show to be related to nitric oxide and prostaglandins production.

Synthesis and antimicrobial activity of 6-triazolo-6-deoxy eugenol glucosides.

A new series of 1,2,3-triazole eugenol glucosides were synthesized. The new compound structures were confirmed by MS, (1)H NMR and (13)C NMR. All of the synthesized compounds were screened for antimicrobial and cytotoxic activity. Five compounds exerted significant activity against the Gram-negative bacteria Salmonella typhimurium with low IC50 values (49.73-68.53 µΜ), and seven compounds were active against the Gram-positive bacteria Micrococcus luteus (42.89-210.94 µM). In vitro cytotoxicity on mouse spleen cells was also evaluated. One compound bearing a phenyl substituent at the triazole ring showed good activity against Salmonella typhimurium (49.73 µM) and low toxicity to normal cells (CC50=157.83 µM). Thus, the compounds herein can be considered for further modification for improving their antibacterial activity or obtaining novel antibacterial drug candidates.