# Antimicrobial and Odour Qualities of Alkylpyrazines Occurring in Chocolate and Cocoa Products
## 3 Antimicrobial Activity of Pyrazines  
Chocolate and cocoa products are well known for their distinguished aroma qualities. One of the most important odour-active groups of compounds present in chocolate is pyrazines. We decided to evaluate the useful biological activities of those good-smelling structures, namely their antibacterial, antioomycete and fungicidal activities. Pyrazines are widely spread in nature. In addition to being found in vegetables, fruits, herbs and heated food--in which they play a key role in the flavour--they also appear frequently in animal and plant life processes: insects produce pyrazines as semiochemicals for inter- and intraspecific communications [35]; 2,5-dimethylpyrazine inhibits the effect of estradiol and plays a volatile pheromone role in rats; pyrazine, methylpyrazine, ethylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, trimethylpyrazine and 2-methoxy-3-methylpyrazine diminish vascularization and the development of embryonic tissue, and reduce oviduct function in mammals [36]. The widespread presence of methoxyprazines in insects has given rise to the hypothesis that they act as all-purpose warning signals of toxic insects [37]. The alkylpyrazines present in cocoa are broadly applied in healthcare. Tetramethylpyrazine, a key ingredient in ligustrazine (an extract of Ligustricum wallichii), is commonly used in Chinese traditional medicine to treat cardiovascular diseases or to enhance blood flow during an ischemic attack in coronary vessels [38]. It was proved that tetramethylpyrazine influences ATP-dependent K\({}^{+}\) channels, tetrodotoxin-resistant Na\({}^{+}\) channels and voltage-dependent Ca\({}^{2+}\) channels. Additionally, it is known to stimulate the  
Figure 2: Alkylpyrazines orthonasal profile of cocoa and dark chocolate. \(\alpha_{1}\)-adrenooreceptors of smooth muscles [36; 39]. By lowering NADPH-oxidase activity in the rat kidney epithelial cell-like cell line NRK-52E, tetramethylpyrazine has antioxidative and anti-inflammatory actions [40]. 2,5-Dimethylpyrazine was found to lengthen the period of therapeutic sleep in mice induced by phenobarbital, as well as to promote GABAergic exoxicity in the mouse's central nervous system. Additionally, rat cognitive abilities are considerably enhanced by tetramethylpyrazine [39]. Due to the recently identified interaction between the corresponding carboxylic acid metabolite and the G-protein coupled receptor GPR109A, 2,5-dimethylpyrazine therapy decreased the plasma levels of nonesterified fatty acids in rats [40]. Derivatives of pyrazine are widely used as medicinally important compounds. The pyrazine ring is a basic setting structure in drug design. There is currently a massive range of therapeutic pyrazine derivatives utilized in the medical field: antimycobacterial (Pyrazinamide, Morinamide, Sulfametopyranoside), antiviral (Favipiravir), anticancer (Bortezomibib, Zibotentan), diuretic (Amiloride, Benzamil), anti-insomnia (Zopiclone, Eszopiclone), antidiabetic (Glipizide), treatment for [PERSON]'s disease (Elenbecestat), insecticide and nematicide (Thionazine), antidandruff (2-Mercaptopyrazine), hypolipidemic (Acipimox), antitumour (Oltipraz), antihepatitis C (Telaprevir), curing smoking addiction (Varenicline), antidepressant (WAY-208,466), \(\mu\)-opioid agonist (Mirfentanil) for pulmonary arterial hypertension as a PGI-2 receptor agonist (Selexipag) and other therapeutic activities are still being researched [41; 42]. Pyrazines have been given GRAS (generally recognized as safe) status by the Flavor and Extract Manufacturers Association (FEMA) for use as flavouring additives in food [43; 44]; they are as well included in the European Union's list of authorized flavouring agents [18], demonstrating that this class of chemicals is a secure substitute for managing and combating microbial contamination. Moreover, around 700 kg of alkylpyrazines are used as flavouring agents annually in the United States, resulting in an estimated average intake of about 37 mg/kg per person [40].