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I ncreasing need in drug consumption during last few decades, lead to the development of the pharmaceutical industry, thus increasing the synthesis of compounds with positive effects on human health. Mass production leads to the increased waste production and environmental pollution. Therefore, emphasis is placed on the green production methods and technologies. In organic synthesis, pollutants can be various solvents as well as catalysts. It is also important to reduce the energy consumption that can be achieved by using ultrasound and microwave irradiation. One of the green approaches in the synthesis is utilization of deep eutectic solvents (DESs), which can be used both as solvents and catalysts. DESs are composed of biodegradable and environmentally benign components. The advantages of the deep eutectic solvents are low toxicity, low inflammability, high availability, high recyclability, low volatility and low price. Among the many desired compounds that are synthesized today, rhodanine derivatives are compounds that have been increasingly synthesized due their significant biological activities such as antibacterial, antimalarial, herbicidal, antifungal, antitumor, insecticidal, antiviral, anti- inflammatory and cardiotonic activities. It has been reported that rhodanine derivatives can potentially be used in the treatment of obesity, cystic fibrosis, diabetes, Alzheimer’s disease, thrombocytopenia, cancer, sleep, mood and central nervous system disorders as well as chronic inflammation. In this work Knoevenagel condensation of salicylaldehydes and rhodanine was conducted under different conditions. Initially, reaction was performed in 20 different DESs at 80 °C in order to find the suitable reaction media. Choline chloride based DESs are synthesized from choline chloride as a hydrogen bond acceptor and 20 different hydrogen bond donors (carboxylic acids, sugars, ureas or amides). The best reaction media was proven to be ChCl:acetamide DES, with the highest product yield of 96.3 %, followed by ChCl:malonic acid, ChCl:levulinic acidand 1, 3- dimethylurea with the yields of 91.1 %, 85.8 % and 80.1 %, respectively. Reaction of rhodanine and salicylaldehyde was performed in four mentioned DESs under microwave and ultrasound irradiation, and with DES as a catalyst in order to find the best reaction conditions.

There are many useful biological properties of pyrazole and its derivatives and they are used in the pharmacy and agrochemical industry, in plant protection products in the form of insecticides and fungicides. Fluorinated 4, 5-dihydro-1H- pyrazole derivatives represent a series of potential new drugs whose antibacterial properties are already being documented. These compounds as also potential new pesticides, and this study aims to determine their impact on the beneficial bacterial soil population. The obtained results determined that a series of tested pyrazole derivatives had no antibacterial inhibitory effect on the tested gram-positive bacterium Bacillus subtilis. This research result is very promising since B. subtillis is a representative of the beneficial bacterial soil population with an important role in soil phosphorus solubilization, siderophore production, plant hormone biosynthesis, and belongs to the group of plant growth - promoting rhizobacteria. Further research is needed which should clarify the impact of these pyrazoles on the growth of other beneficial representatives of soil microorganisms.

The use of propolis in human nutrition dates back to ancient times primarily due to its antibacterial and antiviral properties. Chemical analysis of propolis samples revealed over 300 chemical compounds, the most important groups of which are flavonoids, terpenes and phenols. The chemical composition and properties of propolis significantly depend on the geographical and botanical origin, as well as on the type of bees that collect propolis. The research on Brazilian red and green propolis is constantly growing with the aim of discovering new pharmaceutical preparation that show great activity in antiviral processes. This paper presents an overview of available studies of application of propolis active components in the control and prevention of infectious viruses such as HIV, HSV and others.

Human dipeptidyl peptidase III (hDPP III) is a zinc‐hydrolase that cleaves dipeptides sequentially from the N‐ terminal of different bioactive peptides. Although the physiological role of hDPP III is not yet fully elucidated, its involvement in pathophysiological processes such as mammalian pain modulation and blood pressure regulation emphasizes the need to find new hDPP III inhibitors. Coumarins exhibit a variety of biological activities, and Schiff bases bearing coumarin moiety in conjunction with the imino group (-C=N-) form significant compounds in medicinal and pharmaceutical chemistry. To find new potential inhibitors of hDPP III, in this research we selected 6 coumarinyl Schiff bases to investigate their interactions with hDPP III, combining experimental and computational approaches. hDPP III activity was determined using the spectrophotometric assay, while molecular docking was performed by AutoDock Vina software to obtain information regarding the possible interactions of the strongest inhibitor and hDPP III binding site. The experimental results showed that all analyzed compounds have an inhibitory effect against hDPP III activity at the physiological concentration i.e., 100 μM. The strongest inhibition (87.9 %) has been obtained with compound 5. Docking predicts that 5 interacts with amino acid residues of hDPP III mostly in the region of inter-domain cleft by forming hydrogen bonds with Ile386, His568 and Arg572, π – interactions with Phe109, Pro387 and Ala388, and numerous van der Waals interactions. Most of these residues are found to be constituents of the hDPP III substrate binding subsites S1, S1’, S2, S2’ and S3’. The results of this study provide an insight into the coumarinyl Schiff bases inhibitory activity and interactions toward hDPP III.

Molecular docking study was performed to identify new lead inhibitor of SARS-CoV-2 spike glycoprotein (S protein) from the set of 62 peptide derivatives and evaluate their interactions with the receptor. Peptide-type compounds are previously proven peptide-type SARS- CoV 3CL protease inhibitors. However, highest binding affinity towards S protein has compound 21 (E = -127.2 kcal/mol), which showed the very low inhibitory activity against SARS- CoV 3CL protease. Compound 21 is in conformation that tightly fits along only the subunit S1, making the interactions with RBD and SD2 residues. Formation of a cluster of H- atom acceptor (O and N atoms), allows stronger binding to S1 subdomain. Antiviral drug Remdesivir demonstrated low binding affinity toward the S protein. Compounds that interact with receptor binding domain of SARS-CoV-2 spike glycoprotein may be potential therapeutic targets for drug design against COVID-19.

Prior to comercialization of plant protection products, active components must be evaluated regarding their impact on the enviroment, animal and human health. Toxicity research data must be obtained in a laboratory environment by animal testing for long-term and short-term health effects. The REACH (Registration, Evaluation, and Authorization of Chemicals) guidelines implemented by the European Parliament restrict the overusage of animals in testing, and suggest the application of computational softwares in preliminary toxicity predictions. The aim of this research is to estimate the toxicity of the 10 newly synthetized flourinated pyrazole derivatives as potential compounds in plant protection treatments, as they show great prominence as phosphodiesterase inhibitors, making them possibly applicable as future pesticides. The software used to predict the compound toxicity is the T.E.S.T. (Toxicity Estimation Software Tool) software. Toxicity parameters that were evaluated are: • the lethal doses for rats (oral rat LD50) ; • aquatic toxicity (doses for growth inhibition of Tetrahymena pyriformis and lethal doses that kills half of fathead minnow (Pimephales promelas) ; • mutagenicity of compound that induces revertant colony growth of Salmonella typhimurium ; • bioaccumulation factor (the ratio of the concentration of a chemical in the tissue of an aquatic organism (fish) to its concentration in water.

Honey is one of the most precious natural food substances that has been present in human diet dating back to the mesolithic age. By developing awareness of various health benefits along with the rapid development of apitherapy, honey has become the food of choice regarding the prevention of health problems and improving the immune functions of the human body. It is estimated that by year 2025, the market value of honey production and sales will amount to over $ 10 billion. Honey is currently the third most faked food in the world and it is estimated that 30-35% of total honey that is available on the market is adulterated in some way. The use of various syrups, especially those with a high fructose content along with the false declaration of honey are often used methods that lead to the collapse of the prices of natural honey, endangering the market along with the small producers and ultimately final consumers. Detection and prevention of adulterated honey on the market is the area of interest of many laboratories with accredited methods of honey analysis. Significant advances in artificial intelligence and instrumental detection and their implementation in chemical analysis have made it possible to improve the detection of adulterated honey. This paper provides an overview of modern and modified melisopalinological, instrumental and classical chemical methods of honey analysis for the purpose of detection of adulteration.

Acetylcholinesterase (AChE) is an enzyme responsible for the metabolism of acetylcholine (ACh), the neurotransmitter controlling motor activities in nematodes. Inhibition of AChE results in accumulation of ACh at neuromuscular junctions and leads to paralysis, which makes AChE a good target enzyme for the control of parasitic nematodes. AChE inhibitors used to control parasitic nematodes are mainly organophosphates and carbamates, however, due to their toxicity, they have been withdrawn or have restricted usage. Halogenated pyrazoline derivatives exhibit various biological activities, among them antibacterial, antifungal, and antimicrobial. A series of fluorinated pyrazolines was chosen for the investigation of possible AChE inhibition, using Ellman’s protocol modified for microplate reader. All tested compounds exhibited moderate to good inhibitory effect against AChE at 50 μM concentration, with compound 9 (Fig. 1) having the highest inhibition of 79.5 %. A molecular docking study was performed to gain insight into the binding interaction of compound 9 with AChE (PDB: 2c5g). Results show that compound 9 interacts with amino acid residues located in the peripheral active site of AChE, blocking the narrow passage to the catalytic site. The effect of fluorinated pyrazolines was also tested on two entomopathogenic nematodes, Heterorhabditis bacteriophora, and Steinernema feltiae. Entomopathogenic nematodes are beneficial nematodes used in insect pest management programs because of their resilience to pesticide exposure. Since these nematodes mostly have been unaffected by tested compounds, it indicates their potential use as plant protection agents.

Coumarins and their derivatives demonstrate a wide range of biological activities on different organisms. Recently, some of these compounds have been reported as antifungal agents against several pathogenic fungi and applied in agriculture as eco-friendly plant protection agents. QSAR techniques provide insight into relationships between the chemical structure and biological activity and present an alternative pathway for the design and development of new molecules with improved activity. Using this relationship, QSAR models are used to predict the activity of new or untested compounds. The aim of this study was to reveal the physicochemical and structural requirements of newly synthesized coumarinyl derivatives related to their antifungal activity. Series of coumarinyl derivatives has been tested for antifungal activity on two different fungi: Macrophomina phaseolina and Sclerotinia sclerotiorum at the concentration of 0.8 μmol/mL. Results of antifungal assay were evaluated by QSAR analysis in order to provide insight on the quantitative relationship between chemical structure and antifungal activity of these compounds. Most of the assayed compounds showed moderate to good inhibition of mycelial growth for the both examined fungi. The QSAR study has clarified the importance of the presence of pairs: N – C atoms at the topological distance 5, as well as frequency of the pairs of O – O atoms at the topological distance 4, and N – O at the topological distance 9. Also, the presence of 3D- MorSE descriptor weighted with atomic mass implies of importance of three-dimensional distribution of atomic mass. This research represents initial phase in plant protection product development as it helps design new compounds as potential active components of such products.

Modern strategy for the development of plant protection substances includes computer-aided molecular design as a rational approach used for screening, optimization, and the design of new potent agents in plant protection. Coumarins, secondary plant metabolites and their derivatives demonstrated a wide range of biological activities on different organisms, as well as their applications in agriculture as eco-friendly plant protection agents. Coumarin derivatives have been reported as strong agents against pathogenic species of fungi. Series of 46 novel coumarin derivatives have been evaluated against four pathogen fungi (Macropomina phaseolina, Sclerotinia sclerotiorum, Fusarium oxysporum, Fusarium culmorum). Observed compounds have shown activity against two fungi, M. phaseolina, S. sclerotiorum. Quantitative structure-activity relationships (QSAR) analysis has been performed on obtained experimental data. Since the quality models were not obtained by multiple linear regression (MLR), the artificial neural networks (ANN) analysis was performed using four descriptors appearing in the best MLR models. For the antifungal activity against S. sclerotiorum, ANN analysis was performed using descriptors: 3D- MoRSE (Mor19v) ; Moran autocorrelation (MATS7v) ; relative negative charge (RNCG AM1) ; and E- States, the sum of (- CH2 -) (SssCH2), while for M. phaseolina: geometrical symmetry (SYMM2) ; MATS4m ; MATS5m ; and sum of (= C

Spike surface glycoprotein (S protein) is a component of coronavirus virion particle and it is responsible for viral recognition of Angiotensin Converting Enzyme 2 (ACE2). S protein binds with to human ACE2 and uses it as an entry receptor to invade target cells. S1 subunit is responsible for binding to the host cell receptor, while S2 subunit for the fusion of the viral and cellular membranes. SARS-CoV infection could be blocked by inhibitors that bind to the RBD and induced conformational changes in S glycoprotein and prevents binding to the ACE2. Peptide-type compounds were found to have promising activity against SARCoV. Consequently, these molecules attracted the attention of researchers to prepare and test their more derivatives. In order to screen the abilities for binding to the SARS-CoV-2 spike glycoprotein (S protein) of previously proven peptide-type SARS-CoV 3CL protease inhibitors, we performed the molecular docking study. The three dimensional structure of the SARS-CoV-2 spike glycoprotein in complex with N-acetyl-D- glucosamine as ligand (NAG) (pdb: 6VSB) was downloaded from the Protein Data Bank. Molecular docking was performed on 62 optimized structures of compounds (1-62) and antiviral drug Remdesivir. The highest binding affinity towards S protein has compound 21 (E = -127.2 kcal mol-1). Compound 21 is in conformation that forms a cluster of H-atom acceptor (O and N atoms), which allows stronger biding to S1 subdomain. Antiviral drug Remdesivir demonstrated low binding affinity to the S protein.

Med je jedna od najdragocjenijih prirodnih namirnica koja je u ljudskoj svakodnevici prisutna još od mezolitika. Razvijanjem svijesti o brojnim zdravstvenim benefitima te naglim razvojem apiterapije, med je postao namirnica izbora u prevenciji zdravstvenih problema i poboljšanju imunoloških funkcija ljudskog organizma. Procjenjuje se kako će do 2025. godine tržište proizvodnje i prodaje meda težiti nešto više od 10 milijardi USD. Med je trenutačno treća najpatvorenija prehrambena namirnica na svijetu te se procjenjuje kako je 30-35% ukupnog meda na tržištu na neki način krivotvoreno. Korištenje različitih sirupa, prije svega onih visokog sadržaja fruktoze te lažno deklariranje meda često su korištene metode patvorenja koje dovode do rušenja cijena prirodnog meda ugrožavajući tržište i male proizvođače te konačno i krajnje potrošače. Detekcija te prevencija patvorenog meda na tržištu područje je interesa brojnih laboratorija s akreditiranim metodama analize meda. Značajni napretci na području umjetne inteligencije te instrumentalne detekcije omogućuju poboljšanje detekcije patvorenog meda. Ovaj rad pruža pregled u moderne i modificirane melisopalinološke, instrumentalne i klasične kemijske metode analize meda u svrhu detekcije patvorenja.

Phosphodiesterase type 5 (PDE5) is a cyclic guanosine monophosphate (cGMP)-specific enzyme and mostly expressed in smooth muscle tissue of corpus cavernosum, heart, lung, platelets, prostate, urethra, bladder, liver, brain, and stomach. Inhibitors of PDE5, prevent the hydrolysis of cGMP and become effective treatment to diseases associated with low cGMP level, such as pulmonary arterial hypertension. [1] It has been well-documented that pyrazole- containing compounds diverse chemotherapeutic potentials, such as antileukemic and antiproliferative agents. Beside, halogenated organic compounds has been widely use as many drug candidates. [2] Recently, we have synthesized a novel series of halogenated pyrazolines. Molecular docking study was performed to explain in silico the binding interaction with the PDE5 (PDB: 4oew). Molecular docking has confirmed that compound 5-(2, 6-dimethoxyphenyl)-3-(4-fluorophenyl)-4, 5-dihydro-1H-pyrazole-1-carbaldehyde has lowest total energy binding (-105, 69 kcal/mol). The binding interactions of the most active compound have shown strong hydrogen bonding and van der Waals interactions with the target protein.

The discovery of new and more potent antitumor molecules that act simultaneously on multiple targets is one of the most active fields of research in chemotherapy. The use of methodologies based on cheminformatics, including Quantitative- Structure–Activity Relationship (QSAR) techniques play important role in pharmaceutical design of more efficient antitumor drugs. Also, QSAR analysis is a practical tool for prediction of antitumor activity of new and untested antioxidant. New hybrid molecules with 7- chloroquinoline and arylamidine moieties have been the most effective compounds against leukemia cell lines (K562 and Raji). Antitumor activity was modelled using mono-dimensional (1D), to three- dimensional molecular (3D) descriptors. In order to find a thriving QSAR models for antitumor activities, genetic algorithm- multilinear regression (GA-MLR) was used. The best obtained QSAR models include the following group of descriptors: RDF (Radial Distribution Function) ; GETAWAY (Geometry, Topology, and Atom-Weights AssemblY) descriptors, electronic charge, and information indices. Obtained QSAR models relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules should have increased: three- dimensional distribution of mass in molecules calculated at the radius of 110 Å, atomic distribution at neighbourhood symmetry of 1- order, electric dipole moment along X-axis, as well as more atoms higher electronegativity distributed at the topological distance 3. Based on the conclusions given in the QSAR analysis, a new compounds with possible great antitumor activity were proposed and predicted by means of obtained QSAR models, giving a guidance for further synthesis of new effective quinoline- arylamidine hybrid molecules.

Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease transmitted by tsetse fly (Glossina genus) and caused by kinetoplastid Trypanosoma. We have investigated quantitative structure–activity relationship (QSAR) of anti-trypanosomal activities of natural compounds polyphenols [1], as well as synthetic compounds: pyridyl benzamides, 3-(oxazolo [4, 5-b]pyridin-2- yl)anilides[2], and 6-arylpyrazine-2- carboxamides [3]. Anti-trypanosomal activity was modelled by using mono-dimensional (1D), to three-dimensional molecular (3D) descriptors. In order to find a thriving QSAR models for anti-trypanosomal activities, genetic algorithm-multilinear regression (GA-MLR) and artificial neural networks (ANN) were employed. The GA-MLR QSAR models have excellent statistical robustness with good external predictive ability. For the polyphenols, the obtained models displayed relevance of the frequency of occurrence of two oxygen atoms at topological distance, as well as stability of molecules. The most relevant structural features for the pyridyl benzamides is the presence of oxygen-halogen at a topological distance 6. Derivatives of 3-(oxazolo[4, 5- b]pyridin-2-yl)anilide with enhanced anti- trypanosomal activities should have furan ring and atoms at a topological distance of 7. Inhibitory activity of 6-arylpyrazine-2- carboxamides has correlation with the presence of N-sec-butylformamide and substituted benzene. The results obtained will be useful for further research of more effective plant- derived agents and future synthesized compounds against the Trypanosoma.

Pesticides are toxic chemicals aimed for the destroying pest on crops. Since pesticides with similar properties tend to have similar biological activities, toxicity may be predicted from structure. Their structure feature and properties are encoded my means of molecular descriptors. Molecular descriptors can capture quite simple two-dimensional (2D) chemical structures to highly complex three- dimensional (3D) chemical structures. Quantitative structure-toxicity relationship (QSTR) method uses linear regression analyses for correlation toxicity of chemical with their structural feature using molecular descriptors. Molecular descriptors were calculated using open source software PaDEL and in-house built PyMOL plugin (PyDescriptor). PyDescriptor is a new script implemented with the commonly used visualization software PyMOL for calculation of a large and diverse set of easily interpretable molecular descriptors encoding pharmacophoric patterns and atomic fragments. PyDescriptor has several advantages like free and open source, can work on all major platforms (Windows, Linux, MacOS). QSTR method allows prediction of toxicity of pesticides without experimental assay. In the present work, QSTR analysis for toxicity of a dataset of mixtures of 5 classes of pesticides comprising has been performed. A good number of molecular descriptors were calculated followed by extensive objective and subjective feature selection to avoid redundant descriptors. For model building, the dataset was divided into training (80%) and test (20%) sets. A QSAR model built using three easily interpretable descriptors was subjected to extensive internal and external validation. The QSAR model is statistically robust with R2 = 0.872, Q2 = 0.844, CCCex = 0.845. The analysis revealed that lipophilicity, frequency of occurrence of hydrogen within 3 Å from phosphorus, and the presence of two benzene rings with –CH2– group as linker have good correlation with the toxicity of the pesticides.

What you are holding in your hands is a book of original papers from the international and in- terdisciplinary Symposium CroArtScia2011- Symmetry: Art and Science held in Zagreb, 4-7 May, 2011. It has been published in the CroArtScia Conference Proceedings Series as the first volume covering all areas where the interaction between art and science, and their mutual complementariness and synergy are manifested. The publishers of this volume include: Croatian Academy of Sciences and Arts, Museum of Contemporary Art, Ruđer Bošković Institute, Society of Culture and Art Ivan Filipović, and LASERplus d.o.o. The book opens up a new kind of interdisciplinary research, in which these institutions are involved as equal partners of Sciences and Arts. Each article in the book has been reviewed and proofread separately. The reviewers have been selected from among the leading Croatian and international natural, social, and humanistic scientists.

Varying the substitutive group or substituent position in derivatives of 3, 4-ethylenedioxythiophene (EDOT) such as, bisbenzimidazole amidines, diamidines and pentamidines can modify the potency of their antitumor activity. The aim of this study was to derive a quantitative structure–activity relationship (QSAR) analysis for the antitumor activity of 27 3, 4-ethylenedioxythiophene derivatives against six carcinoma cell lines: AGS (gastric adenocarcinoma) ; MIAPaCa2 (pancreatic carcinoma) ; (CaCo2) colon adenocarcinoma, HEp2 (larynx carcinoma) ; HeLa (cervix adenocarcinoma) ; NCI H358 (bronchioalveolar carcinoma). The goals of the QSAR analysis was to find out which physicochemical and quantum-chemical molecular properties have influence on enhanced antitumor activity The dataset used for building QSAR models consists of 27 molecules whose antitumor activity was measured and described in present and our previously published papers [1-3]. The 2D and 3D molecular descriptors used in this study were calculated by applying the Dragon program (http://146.107.217.178/lab/pclient/). The selection of descriptors based on the best-subset method and the multiple regression analysis (MLR) was performed with the use of STATISTICA 12 (StatSoft, Inc. Tulsa, USA). Splitting data into training test (n = 22) and a test set (n = 5) and calculating the QSAR models and their validation was performed by QSARINS v 2.2 [4]. The best obtained QSAR models include following group of descriptors: BCUT descriptors (BELp6, BELp3) ; WHIM descriptors (G1u, G1p) ; information indices (BIC5) ; 2D autocorrelations descriptors (MATS7e) ; 3D-MoRSE descriptors (Mor19e, Mor15v) ; GETAWAY descriptors (R4u+) ; 2D frequency fingerprint (F09[N-O], F10[C-N]. Results of QSAR analysis suggest that derivates of 3, 4- EDOT with following structural feature may exhibit great antitumor activity: larger molecules with symmetrical arrangement of substituents that allows as much as possible C and N atoms at the located at the topological distance 10, as well as, N and O atoms at the topological distance 9. We constructed a two predictive QSAR models of antitumor activity against gastric adenocarcinoma and pancreatic carcinoma based and estimated the activity of future molecule that may exhibits great activity.

Grape berries, variety Blaufränkish and Zweigelt, produced in two vineyards located in eastern part of Croatia (Slavonia) during 2010- 2012 year were analysed for soluble solid content (SSC), pH, total phenols (TP), total anthocyanins (TA), and antioxidant activity (AOA). The main objective of this study was to investigate the influence of pruning techniques on SSC, pH, TP, TA and AOA. According to analysis of none of the three different ampelotechnical treatments were not resulted in significant difference in pH, soluble solid content, total phenols, total anthocyanins, and antioxidant activity on grape varieties Blaufränkisch and Zweigelt measured at the day of harvest.

The practical importance of the concept of molecular similarity has grown dramatically in recent years. The predominant users are pharmaceutical companies, employing similarity methods in a wide range of applications, when fast, early and reliable prediction of suitable/unsuitable candidate structures is crucial. We were searching for similar molecules by the molecular features like: linear paths, branch points, rings etc. which are hashed in a 1024-bit representation, called “molecular fingerprint“. The Iterative Canonical Form (ICF) introduced by Éena Jakó is a non-conventional graph-based approach to describe Boolean functions. The ICF algorithm takes advantage of the lattice-structure of the n-dimensional Booleanspace, unlike the conventional methods, which are using the standard rules of simplification. In this study we used efficient method for finding a similarity of 69 benzene derivatives with fathead minnow toxicities.

A molecular modelling study was performed on a series of benzimidazo-based inhibitors of human dipeptidyl peptidase III (DPP III). DPP III is a zinc-dependent aminopeptidase with indicated role in pathophysiological processes, such as: pain, ovarian carcinoma, oxidative stress, inflammation and cataractogenesis [1]. Previous research has shown that cyclobutane derivatives containing amidinosubstituted benzimidazole moieties areimportant for the inhibitory activity of human DPP III [2]. Since benzimidazole derivates have shown wide variations in their structures, this study was aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of dipeptiyl peptidase III inhibitors using Quantitative Structure- Activity Relationship (QSAR) analysis. QSAR is a cheminformatic technique for establishing the quantitative relationship between biological activity and descriptors representing physicochemical properties of the compounds in a series using statistical methods. "Two- dimensional" (2D), "three-dimensional" (3D) molecular descriptors, quantum chemical descriptors, and physicochemical parameters, derived from optimised threedimensional structure, have been calculated usingthe Dragon program and HyperChem 8.0. Multiple regression analysis was performed using STATISTICA 7.0. Selection of predictor variables for multiple regression was performed by best-subset method. QSAR is aimed to elucidate the structural features of benzimidazole derivatives required for antagonism of dipeptidyl peptidase III inhibitors. In order to understand the mechanism of the most potent inhibitor binding into the active site of human DPP III we performed docking by AutoDock4 program and molecular dynamicsimulation with the AMBER10 package. The presented study can guide the rational synthesis of novel inhibitors with increased affinity and efficacy.

Grožđe sorata Frankovka i Zweigelt, proizvedeno na području vinogorja Feričanci u razdoblju od 2010. do 2012. godine, bilo je analizirano na ukupne fenole (TP), ukupne antocijanine (TA) i antioksidativnu aktivnost (AOA). Glavni cilj ovog istraživanja bio je utvrditi utjecaj vremena dozrijevanja na sadržaj ukupnih fenola i antocijanina, kao i antioksidativnu aktivnost ; te njihovu povezanost s pH, sadržajem šećera i vremenskim uvjetima (zbroj oborina (TR) i zbroj prosječnih dnevnih temperatura (TDMT)). Dok tijekom zriobe, vrijednost TP uglavnom opada prema statistički značajnim kvadratnim trend modelima, a vrijednost AOA prema linearnim modelima, TA raste linearno. Signifikantna korelacija utvrđena je između TA i sadržaja šećera kod obiju sorata. Za Frankovku, povećane vrijednosti TDMT su snažno utjecale na povećanje TA, sadržaj šećera i pH, kao što su i povećane vrijednosti TR utjecale na povećanje TP. Kod sorte Zweigelt, pozitivna korelacija uočena je između pH i TDMT, te pH i TR. Možemo zaključiti da su vremenski uvjeti snažnije djelovali na istraživane parametre kod sorte Frankovka, nego na sortu Zweigelt.

Umjerena i redovita konzumacija vina povezana je s brojnim blagotvornim učincima vina na zdravlje čovjeka. Ti učinci su povezani s polifenolnim supstancijama iz vina koje imaju najsnažniji utjecaj na bolesti srca i krvnih žila. Polifenolne sastavnice vina su također zaslužne za antikancerogeno, neuroprotektivno i antidijabetičko djelovanje. Na temelju toga, vino, posebice crno može se smatrati funkcionalnom hranom koja ima i dokazano farmakološko djelovanje. Hrvatska obiluje vinorodnim područjima i kvalitetnim vinima, ali su te činjenice slabo iskorištene u marketinške svrhe. Crna vina iz Srednje i Južne Dalmacije imaju najveći sadržaj polifenola, što se pripisuje povoljnijim klimatskim uvjetima koji uvelike utječu na formiranje tih tvari u grožđu tijekom zriobe. Međutim, neka vina iz kontinentalne Hrvatske svojom kvalitetom ne zaostaju za dalmatinskim vinima. Naša vina se moraju istaknuti iz mase stranih, uvoznih vina koja su mahom jeftinija, ali ne nužno i slabije kvalitete od hrvatskih te privući kupca i u našoj zemlji, a posebice u inozemstvu. Navedene činjenice treba maksimalno iskoristiti u strategiji prodaje, distribucije, promocije i marketinga hrvatskih vina.