Scientific context and motivation
    Biogenic Amines (BAs) are known to occur in all living organisms (microorganisms, plants and animals). BAs are the basic nitrogenous compounds with aliphatic, (putrescine, cadaverine, spermine, spermidine), aromatic (tyramine, phenylethylamine), or heterocyclic (histamine, tryptamine) structure. The biogenic amines derived from amino acid tyrosine are called catecholamines because they contain a catechol or 3,4-dihydroxylphenyl group. Catecholamines are hormones released by the sympathetic nervous and adrenal medulla in response to a range of stresses in order to regulate the host physiological functions in living systems. In human body, the most abundant catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine [1-5].
    The universal occurrence of these metabolites in all cells implies that they have an important biological function. Although they have been indentified as necessary for growth, BAs have also been shown to be toxic [6,7].
    Polyamines are important for the growth, renovation, and metabolism of every organ in the body and essential for maintaining the high metabolic activity of the normal functioning and immunological system of gut. Because of polyamines diversity roles in cellular metabolism and growth, the requirement for polyamines is particularly high in rapidly growing tissues. Indeed, the importance of putrescine, spermidine, and spermine in tumour growth is already widely recognized, and the inhibition of polyamine biosynthesis in tumour-bearing individuals is one of the major targets of cancer therapy research [8-10].
    In plants, the diamine putrescine and the polyamines spermidine and spermine are implicated in a number of physiological processes, such as cell division, ?owering, fruit development, response to stress and senescence [11].
    BAs are also related to food spoilage and safety. Consumption of low concentrations of BAs in the average diet is not dangerous, but consumption of high concentrations may result in hypotension (histamine, putrescine, cadaverine), hypertension (tyramine), migraines (tyramine, phenylethylamine), nausea, rash, dizziness, increased cardiac output, and increased respiration. BAs are known to occur in a wide variety of foods, such as fish, meat, dairy, fruits, vegetables, and chocolate [12,13].
    BAs are potential precursors for the formation of carcinogenic N-nitroso compounds. Some BAs such as putrescine, cadaverine, spermidine can act as free radical scavengers. Tyramine has a remarkable antioxidative activity, which increases with its content. Thus, inhibiting effect depends on amino and hydroxy groups. The spermine is able to regenerate tocopherol from the tocopheroxyl radical through hydrogenic donor from amino group. The spermine radical next binds lipid or peroxide radicals into a lipid complex [14,15].
    An antioxidant is a chemical that prevents the oxidation of other chemicals. They protect the key cell components by neutralizing the damaging effects of free radicals, which are natural by-products of cell metabolism. These free radicals attack the nearest stable molecules, stealing its electron. When the attacked molecule loses its electron, it becomes a free radical itself, beginning a chain reaction, finally resulting in the description of a living cell. To protect the cells from the damage caused by oxidants, the organisms have evolved several antioxidant defense mechanisms for rapid and efficient removal of reactive oxygen species from the intracellular environment. In normal circumstances, there is a balance between antioxidants and oxidants. When the equilibrium between oxidants and antioxidant defense systems is imbalanced in favor of the oxidants, the condition is known as oxidative stress. Oxidative stress results in the damage of biopolymers including nucleic acids, proteins, polyunsaturated fatty acids and carbohydrates. Oxidative stress causes serious cell damage leading to a variety of human diseases like Alzheimer’s disease, Parkinson’s disease, atherosclerosis, cancer, arthritis, immunological incompetence and neurodegenerative disorders, etc [16-18].
    Various methods are used to evaluate antioxidant activity of natural compounds in foods or biological systems with varying results. Two free radicals that are commonly used to assess antioxidant activity in vitro are 2,2'-azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). The results are usually expressed as Trolox equivalent antioxidant capacity (TEAC). The methods based on the free radicals are rapid and can be used over a wide range of pH values, in both aqueous and organic solvent systems. It also has good repeatability and is simple to perform; hence, it is widely reported. The oxygen radical absorbance capacity (ORAC) method measures the ability of antioxidants to protect protein from damage by free radicals. In this assay, different generators are used to produce different radicals [19-27].     Quantitative structure–activity and structure-property relationships (QSARs, QSPRs) have been used over the years to develop models for understanding and predicting biological activity or a target property by relating them to chemical structure. These models are particularly useful for screening chemical databases and virtual libraries before the synthesis of chemicals, for setting testing priorities, for reducing reliance on animal testing and, in conclusion, for the timely assessment of the health risks of chemicals. It is widely recognized that QSAR/QSPR equations, derived in a purely empirical fashion from different sets of structural descriptors and experimental data, can give considerable insight into the manner by which chemical structure controls physico-chemical and biological properties of compounds. In this order, the Multiple Linear Regression (MLR), Principal Component Regression (PCR) and Partial Least Squares (PLS) methods have been successfully applied [28-30].     One of the major goals for the physico-chemical screening of chemicals is the prediction of adsorption, distribution, metabolism and excretion (ADME) of the molecule through cellular membranes. There are several routes for a molecule to become absorbed, and the most frequent one is the passive transport through the gut wall, which strongly depends on its solubility in lipids (lipophilicity). Lipophilicity defined as tendency of a chemical compound to distribute between an immiscible non-polar organic solvent and water, is one of the key molecular parameter most frequently used in QSAR/QSPR studies. It plays an important role in several ADME aspects, as well as in the pharmacokinetic and toxicological profile of drugs. Some authors divided the lipophilicity determination techniques in direct and indirect methods. The most known direct method of determination was based on the shake-?ask procedure, but nowadays it was almost totally replaced by the indirect methods such as chromatographic ones, which are more versatile and present some concrete advantages: dynamic process, the consumption of the investigated compounds is minimal, high-purity chemicals and additional analytical quanti?cation are not required. These methods require only the determination of some retention parameters [31-35].
    Classification is useful, since it allows meaningful generalizations to be made about large quantities of data by recognizing among them a few basic patterns. It plays a cardinal role in searching for structures in data. Each of these structures is called cluster or class. A class is a group of individuals (e.g., chemicals, drugs or pixels of an image) which resemble each other more strongly, in terms of particular properties, than they resemble members of other classes.     In classical cluster analysis each object must be assigned to exactly one cluster. This is a source of ambiguity and error in case of outliers or overlapping clusters and affords a loss of information. This kind of vagueness and uncertainty can, however, be taken into account by using the Theory of fuzzy sets. The Theory of fuzzy sets is basically a theory of graded concepts. It provides an adequate conceptual framework as well as a mathematical tool to model the real world problems which are often obscure and indistinct [36-40].
    In the above considerations, the evaluation and modeling of the redox (antioxidant/pro-oxidant) activity and lipophilicity of biogenic amines and related compounds (precursors, metabolites, drugs) are the important research topics for understanding their biological behavior and getting new insights concerning their crucial effects from the perspective of fundamental scientific aspect and new therapeutic approaches. By the proposed objectives and its interdisciplinary, transdisciplinary and holistic nature, the proposed project represents a real support and a consistent contribution to the previous (and future) research studies developed in this area of a large theoretical and practical interest. (List of references, pages 20-23)