Ants use pheromones to coordinate their communal activity. Volatile pyrazines, for instance, mediate food resource gathering and alarm behaviors in different ant species. Here we report that leaf-cutter ant-associated bacteria produce a family of pyrazines that includes members previously identified as ant trail and alarm pheromones. We found that L-threonine induces the bacterial production of the trail pheromone pyrazines, which are common for the host leaf-cutter ants. Isotope feeding experiments revealed that L-threonine along with sodium acetate were the biosynthetic precursors of these natural products and a biosynthetic pathway was proposed.

New derivatives of pyrazolo[3,4-b]pyrazines and related heterocycles were synthesized using 5-amino-3-methyl-4-nitroso-1-phenyl-pyrazole (1) as a starting material. The 5-acetyl derivative 15 was shown to be a useful key intermediate for the synthesis of several derivatives of pyrazolopyrazines. Some of the prepared compounds were evaluated for their anti-inflammatory and anti-breast cancer MCF-7 cell line activities. SAR study showed that compounds 15 and 29 exhibited remarkable anti-inflammatory activity, where 15 showed the same activity as that of the reference drug indomethacin. On the other hand, compounds 25i, 25j showed very significant inhibitory activity (p < 0.001) against MCF-7 breast cancer cell line.

At present, most investigations involving the Maillard reaction models have focused on free amino acids (FAAs), whereas the effects of peptides on volatile products are poorly understood. In our study, the formation mechanism of pyrazines, which were detected as characteristic volatiles in sunflower seed oil, from the reaction system of glucose and lysine-containing dipeptides and tripeptides was studied. The effect of the amino acid sequences of the dipeptides and tripeptides on pyrazine formation was further highlighted. Four different dipeptides and six tripeptides were selected. The results showed that the production of pyrazines in the lysine-containing dipeptide models was higher than that in the tripeptide and control models. Compounds 2,5(6)-Dimethylpyrazine and 2,3,5-trimethylpyrazine were the main pyrazine compounds in the dipeptide models. Furthermore, the C- or N-terminal amino acids of lysine-containing dipeptides can exert an important effect on the formation of pyrazines. In dipeptide models with lysine at the C-terminus, the content of total pyrazines followed the order of Arg-Lys > His-Lys; the order of the total pyrazine content was Lys-His > Lys-Arg in dipeptide models with N-terminal lysine. Additionally, for the tripeptide models with different amino acid sequences, more pyrazines and a greater variety of pyrazines were detected in the tripeptide models with N-terminal lysine/arginine than in the tripeptide models with N-terminal histidine. However, the total pyrazine content and the percentage of pyrazines in the total volatiles were similar in the tripeptide models with the same amino acids at the N-terminus. This study clearly illustrates the ability of dipeptides and tripeptides containing lysine, arginine and histidine to form pyrazines, improving volatile formation during sunflower seed oil processing.

The first catalyst-free post-Ugi cascade methodology was developed for expeditious access to structurally diverse and complex pyrazole-pyrazines in one-pot. This novel cascade reaction features an intramolecular N2-arylation of pyrazoles with allenes at the C-β position of triple bond. Screening in the colorectal cancer cell lines HCT116 and SW620 validated the feasibility of the methodology for generating bioactive compounds. The lead compound 7h which is active against HCT116 and SW620 with IC50 of 1.3 and 1.8 µM, respectively, can be synthesized and purified in a gram process synthetic scale in 7 hours. The mechanical studies indicated that compound 7h can induce cell cycle arrest in the G2/M phase and inhibit proliferation and viability in human colon cancer cells. Overall, compound 7h is represented as a promising starting point for the development of new anti-colorectal cancer drugs.

A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.

Immobilized l-glutamic acid β-methyl ester was sulfonylated with 4-nitrobenzenesulfonyl chloride and alkylated with various α-haloketones. The resulting sulfonamides were reacted with potassium trimethylsilanolate. Then, upon cleavage from the polymer support, tetrasubstituted pyridines were produced as the result of one-step C-arylation, aldol condensation, and oxidation. When cleavage from the resin occurred before the trimethylsilanolate treatment, C-arylation was followed by enamination, which yielded trisubstituted pyrazines. Through the developed protocols, targeted synthesis of novel heterocyclic derivatives was performed using mild reaction conditions and a number of readily available starting materials.

The treatment of hatching eggs relies on classic yet environmentally harmful decontamination methods such as formaldehyde fumigation. We evaluated bacteria-derived volatiles as a replacement within a fundamentally novel approach based on volatile organic compounds (VOCs), which are naturally involved in microbial communication and antagonism due to their high antimicrobial efficiency. Pyrazine (5-isobutyl-2,3-dimethylpyrazine) was applied passively and actively in prototypes of a pre-industry-scale utilization. Altogether, pyrazine decontamination rates of up to 99.6% were observed, which is comparable to formaldehyde fumigation. While active evaporation was highly efficient in all experiments, passive treatment showed reducing effects in two of four tested groups only. These results were confirmed by visualization using LIVE/DEAD staining microscopy. The natural egg shell microbiome was characterized by an unexpected bacterial diversity of Pseudomonadales, Enterobacteriales, Sphingomonadales, Streptophyta, Burkholderiales, Actinomycetales, Xanthomonadales, Rhizobiales, Bacillales, Clostridiales, Lactobacillales, and Flavobacteriales members. Interestingly, we found that especially low pyrazine concentrations lead to a microbiome shift, which can be explained by varying antimicrobial effects on different microorganisms. Micrococcus spp., which are linked to embryonic death and reduced hatchability, was found to be highly sensitive to pyrazines. Taken together, pyrazine application was shown to be a promising, environmentally friendly alternative for fumigation treatments of hatchery eggs.

Increasingly, different heterocyclic systems have been introduced into the steroid nucleus to significantly enhance the antitumor activities of steroid molecules. However, in this study, few literature precedents describing the pyrazine heterocyclic-condensed modification to an A-ring of steroid monomers were found, although the pyrazine group is thought to be essential for the potent anticancer activity of clinically relevant drugs and natural steroid dimers.

An efficient and effective multiple headspace-solid phase microextraction-arrow-gas chromatography-mass spectrometry (MHS-SPME-arrow-GCMS) analytical protocol is established and used to quantify the flavor compounds in oils. SPME conditions, such as fiber coating, pre-incubation temperature, extraction temperature, and time were studied. The feasibility was compared between SPME-arrow and the traditional fiber by loading different sample amounts. It was found that the SPME-arrow was more suitable for the MHS-SPME. The limit of detection (LODs) and limit of quantitation (LOQs) of pyrazines were in the range of 2-60 ng and 6-180 ng/g oil, respectively. The relative standard deviation (RSD) of both intra- and inter-day were lower than 16%. The mean recoveries for spiked pyrazines in rapeseed oil were in the range of 91.6-109.2%. Furthermore, this newly established method of MHS-SPME-arrow was compared with stable isotopes dilution analysis (SIDA) by using [2H6]-2-methyl-pyrazine. The results are comparable and indicate this method can be used for edible oil flavor analysis.

This study evaluated how the generation of pyrazines was promoted by high-intensity ultrasound (HIU) in a Maillard reaction (MR) model system of glucose-glycine. Carbohydrate module labeling (CAMOLA) technique was adopted using D-glucose-13C6 to elucidate the carbon skeleton of both intermediate and final MR products (MRPs). In the D-glucose-13C6-glycine HIU-MR model system, the concentration of 11 types of pyrazines was significantly higher than their counterparts in the thermal MR. Results of CAMOLA analysis showed that a significantly lower proportion of [M]+ in pyrazines with long-length side chains was observed when compared with the pyrazines generated in thermal MR. This phenomenon may suggest the aldol-type condensation was promoted by the HIU, which is a conversion from pyrazines with short-length side chains to those with long-length side chains involving carbonyl compounds. Furthermore, the analysis of isotopomers distribution in 2,3-dimethyl-quinoxaline as the o-phenylenediamine-derivatized 2,3-butanedione indicated that the increased proportion of [M + 4]+ in 2,3-dimethyl-quinoxaline (15.74% ± 0.11%) was attributed to a cleavage of D-glucose-13C6 promoted by the HIU. The above-mentioned findings elucidate that the aldol-type condensation and cleavage of D-glucose contribute to the promoted synthesis of pyrazines. The HIU would generate an extremely high temperature and pressure environment that is favored by the aldol-type condensation as a high-pressure favored reaction. The HIU, therefore, can be further developed as a promising technique to promote flavor generation through the MR.

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (-8.1 ± 0.33 kcal/mol, -8.0 ± 0.35 kcal/mol, and -8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (-6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

The physicochemical properties, fatty acid composition and volatile aroma compounds of cold-pressed passion fruit seed oils were analyzed. The oils were rich in linoleic acid, oleic acid and volatile compounds. A total of 108 volatile compounds including 17 aldehydes, 23 alcohols, 21 esters, 19 ketones, 6 acids, 9 alkenes, 5 pyrazines and 8 others were identified using HS-GC-IMS. The significant differences of volatile compounds in the purple and yellow passion fruit seed oils were observed via the GalleryPlot graph and distinguished by principal component analysis. The results showed that acids, alcohols, esters and ketones were major aromatic compounds in purple passion fruit seed oils, which contribute to flavors such as flowery, fruity, creamy, yogurt. Whereas the contents of aldehydes, pyrazines, alkenes were higher in yellow passion fruit seed oils, which contributes to fatty and nutty odors. The findings filled in our understanding of volatilization characteristics in passion fruit seed oils.

A series of 2-aryl-imidazo-pyridines/pyrazines derivatives has been designed, synthesized and evaluated for their biological activities. Among them, several investigated compounds (1a, 3b and 3d) displayed potent antiproliferative activity against HeLa cell, and also displayed comparable tubulin polymerization inhibitory activity to colchicine. These studies provided a new molecular scaffold for the further development of antitumor agents that target tubulin.

Heterocyclic compounds are organic compounds with heterocyclic structures, which are common in drug molecules. They include pyrazines with diverse functions, including anti-cancer, antimicrobial, antidiabetic, and anticholinergic activities. In this study a new small molecular compound B7 based on tetrazolium substituted pyrazine was synthesized and its effect on the progression of colorectal cancer (CRC) and its potential mechanism were investigated.

This study compared aroma compositions and sensory aroma attributes of raw and cooked Tenebrio molitor larvae (mealworms). Main sensory aroma attributes of raw mealworms were strong wet-soil-like, and less-intense oily, shrimp-like and sweet-corn-like. Quantitatively, the major aroma components of raw mealworms were hydrocarbons and aldehydes. As cooking proceeded, sweet-corn-like, roasted, and fried-oil-like sensory attributes were increasingly perceived with steaming, roasting, and frying, respectively. Some pyrazines, pyrrolidines, and carbonyls increased or appeared in roasted and fried mealworms. Partial least squares regression also showed differences in raw and cooked mealworms based on aroma components and their sensory attributes. Unlike raw mealworms, steamed mealworms had a relatively strong sweet-corn-like aroma attribute, which was related to 2,4,6-trimethyl-heptane, 2,4-dimethyl-dodecane, and 3,5-dihydroxy-6-methyl-2,3-dihydropyran-4-one. In comparison, roasted and fried mealworms exhibited roasted, shrimp-like, and fried-oil-like aroma attributes, which were associated with intermediates of the Maillard reaction and lipid oxidation, such as pyrazines, alcohols, and aldehydes. This result during thermal reactions was very similar to those of meat and/or seafood. The use of mealworms as a savory-type flavor enhancer can be expected.

Plant beneficial rhizobacteria may antagonize soilborne plant pathogens by producing a vast array of volatile organic compounds (VOCs). The production of these compounds depends on the medium composition used for bacterial cell growth. Accordingly, Lysobacter capsici AZ78 (AZ78) grown on a protein-rich medium was previously found to emit volatile pyrazines with toxic activity against soilborne phypathogenic fungi and oomycetes. However, the discrepancy between the quantity of pyrazines in the gaseous phase and the minimum quantity needed to achieve inhibition of plant pathogens observed, lead us to further investigate the volatile-mediated inhibitory activity of AZ78. Here, we show that, besides VOCs, AZ78 cells produce ammonia in increased amounts when a protein-rich medium is used for bacterial growth. The production of this volatile compound caused the alkalinization of the physically separated culture medium where Rhizoctonia solani was inoculated subsequently. Results achieved in this work clearly demonstrate that VOC, ammonia and the growth medium alkalinization contribute to the overall inhibitory activity of AZ78 against R. solani. Thus, our findings suggest that the volatile-mediated inhibitory activity of rhizobacteria in protein-rich substrates can be regarded as a result of multiple factors interaction, rather than exclusively VOCs production.

Aroma compounds in the roasted breasts, thighs and skins of chicken were isolated by solvent-assisted flavor evaporation (SAFE), quantitated by gas chromatography-olfactometry-mass (GC-O-MS), analyzed by aroma extract dilution analysis (AEDA), and determined by recombination-omission tests and sensory evaluation. Forty-seven aroma compounds in total, including aldehydes, ketones, furans, pyrazines, and furanones, were selected by AEDA. Twenty-five compounds were selected as pivotal odorants (Odor Activity Value, OAV ≥ 1). Twenty aroma compounds significantly were identified by recombination and omission experiments. Anethole (fennel odor) was the highest OAV (＞ 1843). Hexanal (grassy) and (E, E)-2,4-decadienal (meaty) were the most abundant aldehydes identified in roasted chicken. 1-octen-3-ol (mushroom), methanethiol (cabbage) and dimethyl trisulfide (areca, sulfur) were considered the key compounds of the breast and thighs of roasted chicken. Notably, furanone and pyrazines, 4-hydroxy-5-methyl-3(2H)-furanone (caramel, sweet and burning odor), 3-ethyl-2,5-dimethylpyrazine (nutty, toasty) and 2,3-dimethyl-5-ethylpyrazine (nutty, toasty) had the most significant effect on roasted chicken odor, especially in the skin.

A total of 84 volatile aroma components were determined in the 9 samples of sugarcane to non-centrifugal sugar (NCS), including 15 alcohols, 12 aldehydes, 10 ketones, 17 carboxylic acids, 11 pyrazines, 7 phenols, 3 esters, 3 hydrocarbons, and 2 sulfur compounds. Of these compounds, 10 were with high flavor dilution (FD) factors based on the aroma extract dilution analysis (AEDA). 4-Hydroxy-2,5-dimethyl-3(2H)furanone exhibited the highest FD factor of 2187, followed by (E)-2-nonenal, 2-hydroxy-3-methyl-2-cyclopentene-1-one, and 4-allyl-2,6-dimethoxyphenol with a FD factor of 729. The odor compounds showed no significant change and were similar to that of sugarcane during the first four steps in the production of non-centrifugal cane sugar. In the middle three stages, the heating slightly affected the aroma composition. Additionally, a prolonged period of high-temperature heating, lead to the production of the Maillard reaction products, such as pyrazines, pyrroles, and furans, differentiating the step to be unique from the previous seven stages. However, the content of the NCS odorants was significantly reduced due to the loss of odor compounds during the drying process.

The volatile compounds from insects (Tenebrio molitor and Zophobas morio larvae) roasted at 160, 180, or 200 °C and fed with potato starch or blue corn flour were isolated by solid-phase microextraction (SPME), and identified by gas chromatography-mass spectrometry (GC-MS). In the tested material, 48 volatile compounds were determined. Among them, eight are pyrazines, aroma compounds that are formed in food products during thermal processing due to the Maillard reaction. Eleven of the identified compounds influenced the roast, bread, fat, and burnt aromas that are characteristic for traditional baked dishes (meat, potatoes, bread). Most of them are carbonyl compounds and pyrazines. To confirm the contribution of the most important odorants identified, their odor potential activity values (OAVs) and %OAV were calculated. The highest value was noted for isobuthylpyrazine, responsible for roast aroma (%OAV > 90% for samples roasted at lower temperatures), and 2,5-dimethylpyrazine, responsible for burnt aroma (%OAV > 20% for samples roasted at the highest temperature). According to the study, the type of feed did not significantly affect the results of the sensory analysis of roasted insects. The decisive influence was the roasting temperature. The highest scores were achieved for Tenebrio molitor larvae heat-treated at 160 °C.

Flavor is one of the most important quality properties of cacao beans, playing a key role in the admissibility of cocoa products, such as cocoa powder. This study examined the industrial processes influencing the flavor of cacao beans. The Ivory Coast cacao beans were used after their alkaline treatment with potassium carbonate (up to pH 7.5-8) and being roasted at 115-120°C for 60-70 min. The volatile components were extracted using Likens-Nickerson simultaneous distillation-extraction (SDE) apparatus. The volatile compound profiles were identified by means of gas chromatography-mass spectrometry (GC-MS), as a result of which several compounds (alcohols, carboxylic acids, aldehydes, ketones, esters, and pyrazines) were recognized. Alkalization and roasting were shown to be two important steps in the cacao beans processing that can affect the final cocoa powder flavor. In addition, pyrazines and esters were two major groups of flavor compounds formed during the roasting stage by the Maillard reaction. The percentage of 2,3,5,6-tetramethylpyrazine was detected in the cacao beans equal to 0.5%. After the liquor pressing stage, tetramethylpyrazine increased to its highest amount (3%) in cocoa powder. It was found that the cocoa powder contained 2.69% of tetramethylpyrazine, 3.22% isobutyl benzoate, and 1.38% linalool. The highest percentage of increase in the mean amounts of 2,3,5,6-tetramethylpyrazine, isobutyl benzoate, and linalool were observed in the roasting stage, after which the percentages diminished.