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The dissertation is structured in three complementary and thematically processed units devoted primarily to the criminalprocedural and criminal aspects of the insight. This dualist character of the insight and the necessary unity of its elements imposed a need to consider both aspects of this institute theoretically. The first part of the paper contains of two chapters. The first one relates to the theoretical-methodological approach and the framework of research, and the second one to theoretical approaches to define the notion of insight and its legal definition, as well as the characteristics of the continental and Anglo-Saxon model of investigation and insights within it, as well as the advantages and disadvantages of both. The second chapter ends with the criminal investigation model in BH, the reasons for its legalization and the problems that arise in practice. The issues related to the insight in the judiciary practice of BH are considered in the second part of the paper. This second part also contains two chapters. The first one refers to the observation of the positive law of BH and its entities – the Federation of BH, the Republic of Srpska and Brcko District, including the competencies of the authorities for conducting the investigation. The second chapter relates to the specificity of the investigation for certain criminal offenses, for proper orientation in conducting the investigation, especially in relation to criminal-technical measures and actions, which shall be individualized and adapted to the conditions and specifics of each particular criminal case (for example, in the case of robbery, murder, rape, arson, etc.). The third part of the paper deals with the probative force of the investigation in the criminal procedure and the values of the investigation activities. The most common mistakes and weaknesses during the survey conduction are separated. An overview and analysis of the research results and conclusions are given at the end of the paper. The aim of the dissertation is to examine and determine the justification of the change in the practice of conducting the investigation, based on the theoretical and empirical indicators obtained from the conducted research, since the model of public prosecution investigation in Bosnia and Herzegovina, as well as its entities – the Federation of BH, the Republic of Srpska and Brcko District of BH, in 2003 was taken over mechanically, without previous valid investigation of the shortcomings and the lack of application of the continental, judicial model of investigation and insights within it. The method of researching social phenomena is used in the research and analysis of this problem. In addition to the use of general methods (method of observation, method of description, method of scientific explanation), the normative method is used too, in order to establish the legal norm for the survey during the scientific work of this topic, as it is prescribed in Bosnia and Herzegovina and implemented in practice. A comparative legal method of legal regulation of insights is also used in judicial and public prosecutorial investigation. An analytical-statistical method and functional analysis are used in the empirical research, where the statistical data of the RS MoI – the number of performed surveys – are processed. The statistical data of the RS Prosecutor's Office on the total number of initiated and completed investigations are provided in order to examine the application insights as evidence in practice, and its impact on the flow and efficiency of the proceedings. The analysis and comparison of statistical data on the number of investigations carried out, their outcome in the three-year observed period of judicial investigation (2000, 2001 and 2002) and the three-year observed period of application of public prosecutor's investigation (2004, 2005 and 2006) has been done. This is done in order to obtain valid indicators regarding the impact which the concept of judicial or prosecutorial investigation has on the quality of investigations in relation to suspensions, accusations and incomplete investigations, and to see how this reflects the effectiveness of the criminal proceedings as a whole. The results of the survey are presented in the second part of the survey (using the questionnaire "opinion" according to the Likert method), which is used as a research technique for collecting peer views and opinions of former investigative judges, current prosecutors, police officers and lawyers on affection or adversity to court or prosecutorial concept of investigation. This kind of research enables the comparison of police activities and investigative judge activities in a pre-trial procedure on the one hand and the investigation conduction in court investigation on the other hand, including the activity of police and public prosecutor in performing the investigation in prosecution investigation. The presented results confirm and undoubtedly indicate that the public prosecutor's investigation contributes more to the efficiency of the procedure than court investigation. Also, the majority of total respondents express affection for the prosecution, which indicates that this research absolutely confirms the justification to introduce prosecution investigations in Bosnia and Herzegovina.

Lactococcus lactis pripada grupi bakterija mlečne kiseline (BMK) i ima dugotrajnu primenu u prehrambenoj industriji kao starter kultura, najviše u proizvodnji tvrdih i polutvrdih sireva. Kako L. lactis ima ključnu ulogu u formiranju ukusa i teksture finalnog proizvoda, a doprinosi i produženju trajnosti namirnica, veliki ekonomski i industrijski značaj doveo je do toga da su laktokoke predmet stalnog izučavanja. Iako se generalno smatraju bezbednim mikroorganizmima, mnogi istraživači ukazuju na činjenicu da laktokoke, kao i druge bakterije mlečne kiseline mogu biti rezervoar gena za rezistenciju. U cilju sprečavanja širenja ovakvih gena na druge bakterije intestinalnog trakta ili patogene bakterije prisutne u hrani, od velikog značaja je izučavanje mehanizama rezistencije, posebno kod laktokoka namenjenih za prehrambenu industriju. Analizom genoma L. lactis detektovano je prisustvo 40 potencijalnih gena za MDR (eng. multidrug resistance) transportere, od čega su svega dva ABC transportera, LmrA i LmrCD i jedan MFS transporter, LmrP funkcionalno okarakterisani. Istraživanja prikazana u ovom radu su imala za cilj da se okarakteriše CmbT (eng. Cysteine and Methionine Biosynthesis Transporter) protein, potencijalno novi MDR transporter u soju L. lactis. Gen cmbT identifikovan je po prvi put prilikom izučavanja regulacije metabolizma sumpora u L. lactis. Primenom različitih kompjuterskih programa, pokazano je da cmbT kodira transmembranski integralni efluks protein (veličine 454 aminokiseline) koji pokazuje homologiju sa članovima 2.A.1.3.X supstrat/H+ antiporter- 2 subfamilije. Prvi korak u funkcionalnoj karakterizaciji CmbT proteina bio je kloniranje i ekspresija cmbT gena pomoću precizno regulisanog NICE (eng. NIsin Controlled gene Expression) sistema... Lactococcus lactis is a lactic acid bacterium (LAB) widely used as a constituent of many industrial and artisanal starter cultures in dairy industry, especially for fermentation of hard and semi hard cheeses. This organism plays a key role in the formation of flavour and texture of cheese and its preservation and because of the great industrial importance it has been the subject of numerous studies. Although they have acquired the „Generaly Regarded As Safe“ (GRAS) status, many investigators have speculated that lactococci as well as other LAB may act as reservoirs of antibiotic resistance genes. The main threat associated with these bacteria is that they can transfer resistance genes to intestinal microorganisms and food-associated pathogenic bacteria. In order to prevent and reduce the spreading of the resistance genes, more studies of multidrug resistance (MDR) transporters in lactococci intended for use in food systems are needed. The genome analysis of L. lactis indicated the presence of at least 40 putative drug transporter genes, but only two ABC transporters, LmrA, and LmrCD, and one MFS transporter, LmrP, have been studied in detail and all three have demonstrated MDR activity experimentally. The aim of this thesis was to investigate and characterize new MDR transporter CmbT (Cysteine and Methionine Biosynthesis Transporter) in L. lactis. The cmbT gene was originally identified from a random mutagenesis study of cysteine and methionine biosynthesis regulation in L. lactis. This gene is predicted to encode an integral membrane efflux protein (454 amino acids) with homology to members of the 2.A.1.3.X drug/H+ antiporter-2 subfamily of the major facilitator superfamily (MFS). In order to follow the transport function of the CmbT protein, the cmbT gene was cloned and over-expressed in L. lactis NZ9000 using the nisin controlled gene expression (NICE) system...

Lactococcus lactis pripada grupi bakterija mlečne kiseline (BMK) i imadugotrajnu primenu u prehrambenoj industriji kao starter kultura, najviše u proizvodnjitvrdih i polutvrdih sireva. Kako L. lactis ima ključnu ulogu u formiranju ukusa iteksture finalnog proizvoda, a doprinosi i produženju trajnosti namirnica, velikiekonomski i industrijski značaj doveo je do toga da su laktokoke predmet stalnogizučavanja. Iako se generalno smatraju bezbednim mikroorganizmima, mnogiistraživači ukazuju na činjenicu da laktokoke, kao i druge bakterije mlečne kiselinemogu biti rezervoar gena za rezistenciju. U cilju sprečavanja širenja ovakvih gena nadruge bakterije intestinalnog trakta ili patogene bakterije prisutne u hrani, od velikogznačaja je izučavanje mehanizama rezistencije, posebno kod laktokoka namenjenih zaprehrambenu industriju.Analizom genoma L. lactis detektovano je prisustvo 40 potencijalnih gena zaMDR (eng. multidrug resistance) transportere, od čega su svega dva ABC transportera,LmrA i LmrCD i jedan MFS transporter, LmrP funkcionalno okarakterisani.Istraživanja prikazana u ovom radu su imala za cilj da se okarakteriše CmbT(eng. Cysteine and Methionine Biosynthesis Transporter) protein, potencijalno noviMDR transporter u soju L. lactis.Gen cmbT identifikovan je po prvi put prilikom izučavanja regulacijemetabolizma sumpora u L. lactis. Primenom različitih kompjuterskih programa,pokazano je da cmbT kodira transmembranski integralni efluks protein (veličine 454aminokiseline) koji pokazuje homologiju sa članovima 2.A.1.3.X supstrat/H+ antiporter-2 subfamilije.Prvi korak u funkcionalnoj karakterizaciji CmbT proteina bio je kloniranje iekspresija cmbT gena pomoću precizno regulisanog NICE (eng. NIsin Controlled gene Expression) sistema... Lactococcus lactis is a lactic acid bacterium (LAB) widely used as a constituentof many industrial and artisanal starter cultures in dairy industry, especially forfermentation of hard and semi hard cheeses. This organism plays a key role in theformation of flavour and texture of cheese and its preservation and because of the greatindustrial importance it has been the subject of numerous studies. Although they haveacquired the „Generaly Regarded As Safe“ (GRAS) status, many investigators havespeculated that lactococci as well as other LAB may act as reservoirs of antibioticresistance genes. The main threat associated with these bacteria is that they can transferresistance genes to intestinal microorganisms and food-associated pathogenic bacteria.In order to prevent and reduce the spreading of the resistance genes, more studies ofmultidrug resistance (MDR) transporters in lactococci intended for use in food systemsare needed.The genome analysis of L. lactis indicated the presence of at least 40 putativedrug transporter genes, but only two ABC transporters, LmrA, and LmrCD, and oneMFS transporter, LmrP, have been studied in detail and all three have demonstratedMDR activity experimentally.The aim of this thesis was to investigate and characterize new MDR transporterCmbT (Cysteine and Methionine Biosynthesis Transporter) in L. lactis.The cmbT gene was originally identified from a random mutagenesis study ofcysteine and methionine biosynthesis regulation in L. lactis. This gene is predicted toencode an integral membrane efflux protein (454 amino acids) with homology tomembers of the 2.A.1.3.X drug/H+ antiporter-2 subfamily of the major facilitatorsuperfamily (MFS).In order to follow the transport function of the CmbT protein, the cmbT genewas cloned and over-expressed in L. lactis NZ9000 using the nisin controlled gene expression (NICE) system...

The mechanism by which central antihypertensives, such as clonidine, rilmenidine, and moxonidine, lower blood pressure is activation of both α2-adrenergic receptors (α2-AR) and imidazoline receptors (IR) in Rostral Ventrolateral Medulla (RVLM), while sedation, as main side effect, is result of activation of only α2-AR in locus coeruleusu. Three imidazoline receptor subtypes, I1-IR, I2-IR, and I3-IR, have been characterized by extensive pharmacological studies. Selective activation of I1-IR is responsible for dose dependant central inhibition of sympathicus and hypotensive effect of the I1-IR ligands. Recent studies indicated that optimal balance between activation of both the I1-IR and α2-AR is crucial factor for strong central hypotensive effect. The second generation of centrally acting antihypertensives, such as rilmenidine and moxonidine, exert higher I1-IR/ α2-AR selectivity and therefore induce fewer side effects than clonidine which mainly activate α2-AR. Also, the selective I1-IR ligands produce antiarrhythmic and diuretic effect too. In the present review we provide a brief update to the field of imidazoline research, highlighting some of the chemical diversity and progress made in the experimental and theoretical studies of the I1-IR ligands. Antihipertenzivi sa centralnim dejstvom, poput klonidina, rilmenidina i moksonidina, ostvaruju svoj farmakološki efekat aktivacijom presinaptičkih α2-adrenergičkih receptora (α2-AR) i imidazolinskih receptora (IR) u Rostral Ventrolateral Medulla (RVLM), dok njihovo sporedno sedativno dejstvo nastaje usled aktivacije samo α2-AR u locus coeruleusu-u. Imidazolinski receptori su na osnovu farmakološkog efekta podeljeni na I1-IR, I2-IR i I3-IR podtip. Ustanovljeno je da selektivna aktivacija I1-IR podtipa imidazolinih receptora dovodi do dozno zavisne centralne inhibicije simpatikusa i sniženja krvnog pritiska. Najnovija istraživanja ukazuju da je optimalana ravnoteža u aktivaciji i I1-IR i α2-adrenergičkih receptora neophodna za postizanje snažnog centralnog hipotenzivnog dejstva imidazolinskih liganada, uz minimalne sporedne efekte. Druga generacija antihipertenziva sa centralnim dejstvom, kao što su rilmenidin i moksonidin, pokazala je veću I1-IR/ α2-AR selektivnost pa samim tim i manje neželjenih efekata nego klonidin koji u najvećoj meri aktivira α2-AR. Pored centralnog hipotenzivnog dejstva, selektivniji I1-IR/ α2-AR ligandi dovode do antiaritmičkog efekta, i podstiču pojačanu renalnu cirkulaciju, diurezu i natriurezu, kao i inhibiciju aktivnosti renalnog simpatikusa. U ovom preglednom radu prikazana je analiza strukturnih karakteristika i farmakofora I1-IR liganada, kao i najnovije eksperimentalne i teorijske studije koje su najviše doprinele napretku u istraživanju I1-imidazolinskih receptora i selektivnijih I1-IR liganada.

Зета потенцијал је дефинисан наелектрисањем површинских молекула и индиректна је метода за одређивање површинског потенцијала бактерија. Ова физичка карактеристика је кључна за одржавање оптималне функције бактеријских ћелија. Поред тога, има кључну улогу у адхезији бактерија за различите супстрате и интеракцији са факторима окружења. Zeta potential is defined by the charge of surface molecules and is an indirect method for determining the surface potential of bacteria. This physical characteristic is crucial for maintaining optimal bacterial cell function. In addition, it plays a key role in bacterial adhesion to various substrates and interaction with environmental factors.

Rezistencija bakterija na delovanje antibiotika predstavlja globalni problem. Na polju razvoja novih lekova iz prirodnih izvora, nedavno je prepoznat potencijal endofitnih gljiva zahvaljujući sposobnosti da proizvedu sekundarne metabolite različitih bioloških aktivnosti. Biosinteza ovih jedinjenja je pod velikim uticajem brojnih faktora koji se vezuju za izbor biljke domaćina, klimatske uslove, ishranu i prisustvo drugih mikroorganizama u okruženju. Velika baza podataka vezanih za aktivnost endofitnih gljiva prema patogenim bakterijama pretaživana je primenom metode analize glavnih komponenti sa ciljem pronalaženja obrazaca u podacima koji bi ukazali na manji broj pravih kandidata za novih razvoj lekova. Na ovaj način, osvetljen je antimikrobni karakter gljive Phomopsis species. In vitro testovima je potvrđeno da dihlormetanski ekstrakt gljive izolovane iz četina bora inhibira rast bakterija Escherichia coli i Staphylococcus aureus. Hromatografsko razdvajanje pojedinačnih jedinjenja ekstrakta optimizovano je primenom dizajna eksperimenata, a zatim je izvršeno izolovanje i karakterizacija njihove hemijske strukture korišćenjem masene spektrometrije i NMR spektroskopije. In silico metodama su definisani prediktori bioraspoloživosti i toksikološke aktivnosti jedinjenja (Z)-(Z)-2-acetoksiprop-1-en-1-il-3-(3-((E)-3,4-dihidroksipent-1-en-1- il)oksiran-2-il)akrilat i (Z)-(Z)-2-acetoksiprop-1-en-1-il-(3-((E)-4-hidroksi-3-oksopent-1-en-1- il)oksiran-2-il)akrilat. Za razliku od dosadašnih istraživanja koja su se ograničavala in vitro testovima antimikrobne aktivnosti endofitnih gljiva i razrešavanjem hemijske strukture izolovanih biomolekula, ova disertacija predstavlja proširenje prethodnih istraživanja primenom in silico metoda. Studija molekulskog dokinga omogućila je razumevanje mehanizama interakcije biomolekula sa receptorima koji pripadaju patogenim bakterijama uobičajeno multirezistentnim na antibiotike. Primenom veštačkih neuronskih mreža nagrađeni su pouzdani modeli koji ukazuju na vezu između hemijske strukture, parametara interakcije i afiniteta vezivanja za receptore na osnovu kojih je moguć razvoj novih hemijski srodnih antibiotika. Bacterial resistance towards antibiotics represents a global phenomenon. Potential of endophytic fungi as producers of secondary metabolites with wide spectra of different bioactivities in the field of drug discovery from natural resources has recently been introduced. The production of these compounds is under great impact of variety of factors related to the choice of plant host, climate conditions, nutrition and presence of other microorganisms in the same surrounding. Big data set comprising of indices of endophytic fungi antibacterial activity towards patogen bacteria was evaluated using principal component analysis with the aim to find patterns in data and to point out to a limited number of proper candidates for future pharmaceutical research. This resulted in highlightening of the antimicrobial character of Phomopsis species. In vitro tests proved that dichloromethane extract of endophytic fungi isolated from conifer needles inhibits the growth of Escherichia coli and Staphylococcus aureus. Chromatographic separation of individual components of extract was optimized using design of experiments followed by the isolation and chemical structure characterization using mass spectrometry and NMR spectroscopy. In silico methods were used to define the predictors of bioavaliability and toxicological activity of compounds (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3- (3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate and (Z)-(Z)-2-acetoxyprop-1-en-1- yl-3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate. Unlike up to date research outcomes limited to in vitro evaluation of antimicrobial activity of endophytic fungi and chemical structure elucidation of isolated biomolecules, this disertation represents an extension to previous investigations using in silico methods. The molecular docking study enabled the comprehensive understanding of the mechanisms underlying the interaction of biomolecules with receptors belonging to usually multidrug resistant bacterial pathogens. The artificial neural networks were used to build reliable models relating chemical structure, parameters of interaction and the binding affinity to receptors, thus providing the essence for future development of new chemically related antibiotics.

Predmet naučnog istraživanja ove doktorske disertacije ,,In silico selekcija i in vitro ispitivanje prirodnih i sintetskih jedinjenja sa potencijalnom inhibitornom aktivnošću na rast Leishmania spp." su prirodna i sintetska jedinjenja sa potencijalnim inhibitornim dejstvom na protozoe iz roda lajšmanija. Osnovni zadatak studije je bio da se in silico metodologijom pronađu odgovarajući kandidati koji pripadaju takvoj grupi jedinjenja i da se njihova aktivnost potvrdi in vitro eksperimentima. Dodatni zadatak je bilo postavljanje hipoteze o mehanizmu dejstva inhibitora na ciljna mesta u telu parazita na osnovu razumevanja interakcija hemijskih jedinjenja kandidata i odabranih metaboličkih enzima. Stečena saznanja imaju za cilj da doprinesu razvoj i dizajn novih aktivnih jedinjenja koja imaju potencijalnu hemoterapijsku primenu u lečenju lajšmanioze sa minimalnim toksičnim dejstvom na ćelije domaćina. Prva faza istraživanja obuhvata: (1) Definisanje kriterijuma za virtuelni skrining baza hemijskih jedinjenja upotrebom molekulskih deskriptora: elektron-jon interakcionog potencijala – EIIP i prosečnog kvazivalentnog broja – AQVN, 3D modela odnosa strukture i aktivnosti – 3D-QSAR i farmakofornog 3D modela zasnovanog na strukturi liganda; (2) Primena homolognog modelovanja enzima čija struktura nije kristalografski utvrđena; (3) razvoj kombinovanog protokola za virtuelni skrining zasnovanog na strukturi liganda i enzma u cilju dobijanja novih inhibitora rasta lajšmanije; (4) In silico skrining anti-targeta, tj. ispitivanje interakcija potencijalnih inhibitora sa enzimima koji učestvuju u njihovom metabolizmu i koji su prisutni u ćelijama domaćina; (5) Predviđanje apsorpcije, distribucije, metabolizma, ekskrecije i toksičnosti – ADMET i fizičkohemijskih osobina kandidata. Druga faza istraživanja obuhvata: (1) Odabir kandidata sa potencijalnom aktivnošću na lajšmanije na osnovu in silico skrininga, a koji se mogu pronaći u katalogu dobavljača ili koji se pronalaze u dostupnoj bazi prirodnih proizvoda; (2) Dobijanje odabranih kandidata automatizovanom sintezom; (3) In vitro ispitivanje aktivnosti inhibitora porekla na Leishmania spp. Definisan je protokol virtuelnog skrininga, a potom primenjen za pretragu baze MetIDB od 5.667 jedinjenja, upotrebom EIIP/AQVN filtera i 3D-QSAR. Jedinjenja sa najboljim rezultatima pretrage su potom dokovana u model humane i arginaze lajšmanije kao i anti-target modele koje čine citohromi P450 familije enzima 2a6, 2c9, 3a4, sulfotransferaza i pregnan-X-receptor sa ciljem označavanja neželjenih receptor-ligand interakcija u toku metabolizma. Upotreba ove metode utiče na donošenje odluke o odabiru kandidata koji potencijalno imaju umanjena toksična i neželjena dejstva u toku lečenja lajšmanioze. Pripremljena je serija novih sintetskih jedinjenja, derivata oksadiazola i indolizina. Za ova jedinjenja su izračunati EIIP i AQVN deskriptori na osnovu kojih je formiran domen za upotrebu u narednom koraku, tj. skriningu zasnovanom na strukturi liganda. Najbolji kandidati su dokovani u model humane arginaze i finalno okarakterisani na osnovu dokinga u grupe anti-target enzima, kako bi se ispitala mogućnost interakcije sa proteinima esencijalnim za njihov metabolizam. Osam kandidata je testirano in vitro. Rezultati pokazuju da antilajšmanijalna aktivnost postoji za tri od osam kandidata. Najbolji kandidat sa 2,18 μM IC50 na amastigote Leishmania donovani u makrofagama, predstavlja interesantnu strukturu za razvoj novih agensa sa dejstvom na lajšmanije. Primenom strukturnih podataka izozima, modelovana je 3D struktura Leishmania infantum alternativne NADH dehidrogenaze (tip 2) upotrebom metoda prepoznavanja homologa. Virtuelnim skriningom je izvršena pretraga potencijalnih inhibitora koji kao ciljno mesto dejstva imaju LiNDH-2 ubikvinon-vezivno mesto... he subject of this dissertation titled: "In silico selection and in vitro testing of natural and synthetic compounds inhibitors of Leishmania spp growth" is the natural and synthetic compounds that act as growth inhibitors of the protozoa of the genus Leishmania. The main objective of this study is to identify such compounds using in silico methodology and evaluate the activity by in vitro experiments. A further aim is to hypothesize the mechanism of action against specific targets within the parasite body, based on an understanding of molecular interactions with specific metabolic enzymes. These research findings should be used to develop targeted drugs against leishmaniasis that reduce the risk of toxic effects on host cells. The first phase consists of (1) defining the criteria for virtual screening of compound databases using the descriptors: electron-ion interaction potential – EIIP and average quasivalence number - AQVN, quantitative structure-activity relationship - 3D-QSAR and ligand-based pharmacophore model. (2) The application of homology modeling to elucidate target structure necessary for receptor-ligand interactions with parasite and the host, for those enzymes for which crystallographic structure is not available; (3) The development of VS protocol comprising ligand-based and structure-based methods to obtain inhibitors of Leishmania growth; (4) In silico anti-target screening, viz.i.e. qualification of receptor-ligand interactions of the potential inhibitors against host metabolic enzymes; (5) The prediction of absorption, distribution, metabolism, excretion and toxicity - ADMET and physicochemical properties of the selected candidates. The second phase of research involves: (1) the selection of candidates with potential activity against leishmaniasis based on in silico screening, found in the supplier's catalog or in the available database of natural products; (2) the extraction of selected candidates by automated synthesis; (3) the in vitro study of the inhibitory activity of Leishmania spp. After defining VS protocol, an initial screening was performed using an EIIP/AQVN filter and 3D-QSAR against the MetIDB database of 5,667 compounds. Top hits were screened in silico against human and Leishmania arginase and an anti-target model consisting of cytochromes P450 2a6, 2c9, 3a4, sulfotransferase, and the pregnane X receptor to flag unfavorable ligand-protein interactions during compound metabolism. Using this method as a filter affects the decision of choosing compounds which may produce fewer toxic and adverse effects in the treatment of leishmaniasis. A series of novel oxadiazoles and indolizine-containing compounds were synthesized. Then, EIIP and AQVN values were calculated for each compound and only those that belonged to a predefined domain during ligand-based virtual screening were selected. Molecular docking of the selected candidates using a parasite arginase model was performed. The top hits were further docked to human arginase and characterized by docking to anti-target enzymes to mark their possible interactions with enzymes essential for their metabolism. Eight candidate compounds were selected for further experimental testing. The results show measurable in vitro anti-leishmanial activity for three out of eight compounds...

Пандемија изазвана SARS-CoV-2 вирусом узроковала је притисак на здравствени систем широм света, изискујући различите стратегије у превенцији ширења инфекције. Вакцинација се сматра најзначајнијом процедуром за постизање колективног имунитета, али успешност спровођења имунизације зависи од прихватања вакцинације у популацији. The SARS-CoV-2 pandemic has put pressure on health system around the world, demanding different strategies to prevent the spread of infection. Vaccination is considered to be the most important procedure for achieving collective immunity, but effectivness of immunization depends on population’s acceptance of vaccination.

U ovoj doktorskoj disertaciji ispitane su protolitičke ravnoteže i ravnoteža(Z)/(E)- izomerizacije devet ACE inhibitora (kaptopril, cilazapril, fosinopril, lizinopril, perindopril, ramipril, kvinapril, zofenopril) u micelarnim rastvorima surfaktanata različitog naelektrisanja, anjonskog (natrijum-dodecilsulfat, SDS), katjonskig (cetiltrimetilamonijum-bromid, CTAB)i nejonskog (4-oktilfenolpolietoksilat, TX 100)... In this doctoral dissertation the protolytic equilibria and the (Z)/(E)equilibria of nine ACE inhibitors (captopril, cilazapril, fosinopril, lisinopril, perindopril, ramipril, quinapril and zofenopril) were investigated in micellar solutions of differently charged surfactants, anionic (sodium-dodecyl - SDS), cationic (cetyltrimethyilammonium-bromide, CTAB)and nonionic (4-octylphenol polyetoxylate, TX 100)...