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Lithium disilicate CAD/CAM endocrown of endodontically treated premolar restored with MOD filling - case report
No full textEndodontski liječeni zubi često imaju značajno kompromitiranu strukturu zbog opsežnih
karijesnih lezija, fraktura i mehaničkih oštećenja nastalih tijekom terapije. Gubitak marginalnih
grebena i smanjena otpornost na lom, zahtijevaju pažljivo planiranje protetske rehabilitacije.
Tradicionalna rješenja, poput intrakanalnih kolčića i klasičnih krunica, pokazala su određena
ograničenja, osobito zbog dodatnog oslabljenja zuba i rizika od frakture korijena. Razvojem
CAD/CAM tehnologije i adhezivnih sustava, endokrunice su se istaknule kao suvremeno
rješenje koje omogućuje očuvanje veće količine zubne strukture, bolju raspodjelu žvačnih sila
te uz to, dobra estetska svojstva. Endokrunica je jednodijelni bezmetalni fiksnoprotetski
nadomjestak koji nadomješta koronarni dio zuba, sidri se u pulpnoj komorici bez ekstenzije u
korijenske kanale, a mikroretenciju ostvaruje adhezivnim mehanizmom. Upravo ta minimalno
invazivna priroda čini je pogodnom za širok raspon kliničkih situacija, osobito kada anatomski
ili morfološki uvjeti onemogućuju izradu klasične preparacije.
Endokrunice omogućuju jednostavniji, brži i precizniji protetski postupak, posebno kada se
izrađuju CAD/CAM tehnologijom. Korištenje adekvatnih materijala, poput litij-disilikatne
keramike, dodatno doprinosi njihovoj trajnosti i estetici, uz dobru otpornost na funkcionalna
opterećenja.Endodontically treated teeth often have a significantly compromised structure due to extensive
carious lesions, fractures and mechanical damage caused during therapy. The loss of marginal
ridges and reduced fracture resistance require careful prosthetic rehabilitation planning.
Traditional solutions, such as intracanal posts and classic crowns, have shown certain
limitations, especially due to additional weakening of the tooth and the risk of root fracture.
With the development of CAD/CAM technology and adhesive systems, endocrowns have
emerged as a modern solution that allows for maximal preservation of tooth structure, better
distribution of occlusal forces and favorable aesthetic properties. An endocrown is a single
piece metal-free fixed prosthetic restoration that replaces the coronal part of the tooth, it is
anchored in the pulp chamber without extension into the root canals, and achieves
microretention via adhesive mechanisms. It is precisely its minimally invasive nature that
makes it suitable for a wide range of clinical situations, especially when anatomical or
morphological factors preclude traditional preparations.
Endocrowns enable a simpler, faster and more precise prosthetic workflow, especially when
they are made with CAD/CAM technology. The use of appropriate materials, such as lithium
disilicate ceramics, further enhances their durability and esthetics, along with providing optimal
resistance to functional stress
Improving the assembly process by applying lean management tools
No full textU ovom radu opisan je koncept lean menadžmenta te su detaljnije objašnjeni temeljni principi i najčešće korišteni alati lean menadžmenta u autoindustriji. Posebna pozornost obratila se gubitcima koji se javljaju u proizvodnim procesima. Nakon teoretskog dijela prikazani su rezultati mjerenja količine vremena potrebnog za montažu automobila na odabranom primjeru iz prakse. Rezultati mjerenja potom su se analizirali te su identificirani gubitci koji se javljaju. Kako bi se smanjila potrebna količina vremena montaže napravljena je optimizacija montažne linije te su predložene daljnje mjere za unaprjeđenje.This thesis deals with the concept of Lean management and further explains its fundamental principles, as well as its most frequently used tools within the auto-industry. A particular emphasis is put on the losses that emerge during production. Following the theoretical concept of Lean management, this research shows measuring results where the object of question was the amount of time needed to assemble a car seen in the chosen example. The measuring results were consequently analysed and have identified the occuring losses. In order to reduce the amount of time needed for assembly, an optimisation o fan assembly line was produced and further developoing aspects were suggested
Application of HRN EN 15085 standard requirements in manufacturing of transformer casing structure
No full textU ovom radu provedena je specifikacija proizvodnih zahtjeva za izradu zavarene konstrukcije transformatorskog kotla prema normi HRN EN 15085. Norma postavlja opće smjernice za zavarivanje željezničkih vozila i komponenti. U tekstu su detaljno razmatrani zahtjevi norme te je posljedično izrađen plan kontrole i inspekcija uključujući dodatne zahtjeve naručitelja sa stanovišta izrade radnih proba. U eksperimentalnom dijelu na određenim sekcijama transformatorskog kotla provedena su odgovarajuća ispitivanja, sukladno definiranom planu kontrole. Prikazana su tražena izvješća i dokumentacija sukladno normom HRN EN 15085. Zaključno, provedena je analiza kritičnih mjesta u proizvodnji zavarivanjem koja imaju najveći utjecaj na kvalitetu proizvoda te je ocijenjena prikladnost postojećeg sustava za primjenu zahtjeva HRN EN 15085.In this final thesis, the specification of production requirements for the fabrication of a welded construction of a transformer tank was carried out according to the standard HRN EN 15085. The standard provides general guidelines for welding railway vehicles and its components. The text thoroughly discusses the standard requirements, and consequently, an Inspection and testing plan is developed, including additional requirements from the client’s perspective regarding the creation of working samples. In the experimental part of thesis, appropriate tests were conducted on specific sections of the transformer tank, in accordance with the defined control plan. The required reports and documentation are presented in accordance with the HRN EN 15085 standard. In conclusion, an analysis of critical welding points in the production was conducted, identifying those with the greatest impact on product quality, and the suitability of the existing system for implementing the HRN EN 15085 requirements was assessed
Coumarin derivatives of 1,2,4-triazole - synthesis and biological activity related to plant protection application
No full textU okviru doktorskog rada sintetizirani su kumarinski 1,2,4-triazoli s mogućim višestrukim biološkim učincima vezanim za primjenu u zaštiti bilja. Sinteza je provedena kao one-pot reakcija kumarinskih hidrazida (1 – 3) i različito supstituiranih izotiocijanata u niskotemperaturnom eutektičkom otapalu kolin-klorid : urea (molni omjer 1 : 2), miješanjem na magnetskoj miješalici pri 80 °C. Rezultat su tri serije spojeva: prva, u kojoj je
1,2,4-triazolni prsten povezan -CH2- poveznicom na položaju 4, a hidroksilna je skupina na položaju 7 kumarina (1a – k), te druga serija derivata s 1,2,4-triazolnim prstenom povezanim eterskom poveznicom na položaju 7 kumarina i metilnom skupinom na položaju 4 kumarina (2a – o). Treća, dodatna serija derivata od druge se razlikuje po nedostatku metilne skupine na položaju 4 kumarina (3a – h). Korištenje niskotemperaturnog eutektičkog otapala omogućilo je provođenje reakcije u jednom stupnju, bez primjene katalizatora i organskih otapala štetnih za okoliš. Zbog pojednostavljene izolacije i pročišćavanja produkata, skraćeno je vrijeme trajanja postupka u odnosu na konvencionalnu i druge objavljene metode. Derivati kumarinskih 1,2,4-triazola su dobiveni u prinosima od 25 do 91 %, a njihove su strukture potvrđene masenom spektrometrijom te 1H i 13C NMR spektroskopijom. Svim priređenim spojevima računalno je procijenjena sličnost s pesticidima te toksičnost za čovjeka i okoliš. Utvrđeno je kako većina spojeva ima povoljan toksikološki profil u odnosu na komercijalne triazolne pesticide. Antifungalno djelovanje in vitro ispitano je na četiri fitopatogene gljive, a antibakterijsko djelovanje na dvije fitopatogene i dvije zemljišno-korisne bakterije. Kumarinski 1,2,4-triazoli uspješno su inhibirali rast micelija gljiva, s izraženim antifungalnim djelovanjem druge serije derivata na Sclerotinia sclerotiorum i Fusarium oxysporum. Sintetizirani spojevi nisu imali antibakterijski učinak ni na patogene ni na zemljišno-korisne bakterije. Na temelju rezultata antifungalnog djelovanja provedena je analiza kvantitativnog odnosa strukture i aktivnosti (QSAR) spojeva. Model za djelovanje na S. sclerotiorum razvijen je pomoću tri deskriptora (nR=Ct, RDF095m i HATS1e) i može objasniti 79 % inhibitornog djelovanja kumarinskih 1,2,4-triazola. Model za djelovanje na F. oxysporum razvijen je pomoću četiri deskriptora (R4u+, nAROR, RDF080e i Mor11u), a može objasniti 77 % inhibitornog djelovanja spojeva. Pouzdanost razvijenih modela potvrđena je metodama unutarnje i vanjske procjene valjanosti. Potencijalni mehanizam antifungalnog djelovanja istražen je metodom molekulskog uklapanja spojeva u enzime važne za rast micelija (sterol 14α-demetilazu, hitinaze A i B, N-miristoil transferazu) te enzime potrebne za razaranje stanične stijenke domaćina (proteinazu K, endoglukanazu I te endopoligalakturonaze I i II). Spojevi su se dobro uklopili u aktivna mjesta demetilaze, hitinaza A i B, proteinaze K te endopoligalakturonaza I i II. Unatoč dobrim energijama uklapanja, spojevi nisu uspjeli ostvariti interakcije u aktivnim mjestima N-miristoiltransferaze i endoglukanaze. Iz dobivenih rezultata može se zaključiti kako su derivati druge serije kumarinskih triazola potencijalni inhibitori demetilaze, obje hitinaze ili proteinaze K, dok su derivati prve serije spojeva inhibitori endopoligalakturonaza. Spoj 2j ističe se svojim antifungalnim djelovanjem i procjenjenom niskom toksičnosti, što ga čini dobrim kandidatom za razvoj novog aktivnog sastojka sredstava za zaštitu bilja.In this doctoral thesis, coumarin 1,2,4-triazoles with potential multiple biological effects related to application in plant protection were synthesized. The synthesis was carried out as a one-pot reaction of coumarin hydrazides (1 – 3) and differently substituted isothiocyanates in a deep eutectic solvent, choline chloride : urea (molar ratio 1 : 2), by stirring with a magnetic stirrer at 80 °C. The result is three series of compounds: the first in which the 1,2,4-triazole ring is connected by a -CH2- linker at position 4 and the hydroxyl group is at position 7 of the coumarin (1a – k), and the second series of derivatives with a 1,2,4-triazole ring connected by an ether linker at position 7 of the coumarin and a methyl group at position 4 of the coumarin (2a – o). The third, additional series of derivatives, differs from the second by the absence of a methyl group at position 4 of coumarin (3a – h). The use of a deep eutectic solvent enabled to carry out the reaction in one step without the need to use catalysts and environmentally harmful organic solvents. The simplified isolation and purification of the products shortened the duration of the process compared to conventional and other published methods. The derivatives of coumarin 1,2,4-triazoles were obtained in yields of 25 to 91 %, and their structures were confirmed by mass spectrometry and 1H and 13C NMR spectroscopy. All prepared compounds were evaluated in silico for their similarity to pesticides and their toxicity to humans and the environment. Most of the compounds were found to have a favorable toxicological profile compared to commercial triazole pesticides. The antifungal activity was tested in vitro on four phytopathogenic fungi, and the antibacterial activity on two phytopathogenic and two soil-beneficial bacteria. Coumarin 1,2,4-triazoles successfully inhibited the growth of fungal mycelia, with the second series of derivatives showing pronounced antifungal activity on Sclerotinia sclerotiorum and Fusarium oxysporum. The synthesized compounds did not show antibacterial activity, neither on the pathogens nor on the soil-beneficial bacteria. Based on the results of antifungal activity, a quantitative structure-activity relationship (QSAR) analysis of the compounds was performed. The model for the effect on S. sclerotiorum was developed using three descriptors (nR=Ct, RDF095m and HATS1e) and can explain 79 % of the inhibitory effect of coumarin 1,2,4-triazoles. The model for the effect on F. oxysporum was developed using four descriptors (R4u+, nAROR, RDF080e and Mor11u) and can explain 77 % of the inhibitory effect of the compounds. The reliability of the developed models was confirmed by internal and external validation methods. The potential mechanism of antifungal activity was investigated by means of molecular docking of the compounds to the enzymes important for mycelial growth (sterol 14α-demethylase, chitinases A and B, N-myristoyltransferase) and enzymes necessary for host cell wall destruction (proteinase K, endoglucanase I and endopolygalacturonase I and II). The compounds fit well into the active sites of demethylase, chitinases A and B, proteinase K, and endopolygalacturonase I and II. Despite good fitting energies, the compounds failed to achieve interactions in the active sites of N-myristoyltransferase and endoglucanase. From the obtained results, it can be concluded that the derivatives of the second series of coumarin triazoles are potential inhibitors of demethylase, chitinases or proteinase K, while the derivatives of the first series of compounds are inhibitors of endopolygalacturonases. Compound 2j stands out for its antifungal activity and its estimated low toxicity, which emphasized it as a good candidate for the development of a new active ingredient for plant protection products
Selective degradation of misfolded proteins in quiescent yeast Saccharomyces cerevisiae
No full textKako bi se zaštitile od nakupljanja pogrešno smotanih proteina, stanice su razvile mehanizme za kontrolu kvalitete proteina, uključujući put selektivne razgradnje sustavom ubikvitin-proteasoma. Prethodna istraživanja kontrole kvalitete proteina uglavnom su provedena u stanicama koje se aktivno dijele, međutim mnoge stanice, poput neurona i matičnih stanica u mirovanju, se ne dijele. U ovoj disertaciji istražili smo puteve selektivne razgradnje proteina u stanicama u mirovanju, koristeći modelni organizam, kvasac Saccharomyces cerevisiae. Po ulasku stanica kvasca u mirovanje aktivira se autofagija, a veliki dio proteasoma reorganizira se u granule u kojima proteasomi vjerojatno nisu aktivni, stoga nije bilo jasno oslanjaju li se stanice u mirovanju na sustav ubikvitin-proteasoma za eliminaciju pogrešno smotanih proteina. U ovom radu uspostavili smo ekspresiju modelnih pogrešno smotanih proteina tGnd1, stGnd1 i Ubc9ts u stanicama u mirovanju, koristeći PIR3- i Z-promotore. Pokazali smo da stanice u mirovanju prepoznaju pogrešno smotane proteine te ih usmjeravaju u selektivnu razgradnju, čak i u kasnijim fazama mirovanja. Nadalje, razgradnja je ovisila o aktivnosti E3 ligaza ubikvitina Ubr1 i San1, te proteasomu, što upućuje na sličan put razgradnje kao u proliferirajućim stanicama. Sveukupno rezultati pokazuju da stanice kvasca u mirovanju zadržavaju funkcionalnu kontrolu kvalitete proteina, te da se ona primarno temelji na selektivnoj razgradnji proteina.To prevent the negative impact of misfolded protein accumulation, cells have developed protein quality control pathways, including selective degradation by the ubiquitin-proteasome system. Previous research on protein quality control has mostly been conducted in actively dividing cells. However, many cells, such as neurons and quiescent stem cells, are non-dividing. In this thesis, we investigated selective protein degradation in quiescent cells, using yeast Saccharomyces cerevisiae as a model organism. Upon entry into quiescence, yeast cells induce autophagy, and a large portion of the proteasomes relocalizes into cytoplasmic granules, presumably in an inactive form. Therefore, it has been unclear whether quiescent cells rely on the ubiquitin-proteasome system for the elimination of misfolded proteins. In this study, we established an expression system of model misfolded proteins tGnd1, stGnd1, and Ubc9ts in quiescent cells using PIR3- and Z-promoters. We show that quiescent cells recognize misfolded proteins and direct them to selective degradation, even in the later stages of quiescence. Furthermore, degradation was dependent on the E3-ubiquitin ligases Ubr1 and San1 and the proteasome, suggesting a similar pathway as in proliferating cells. Overall, the results show that quiescent yeast cells maintain functional protein quality control, which is primarily based on selective protein degradation
Morphological changes of beaches in Makarska littoral
No full textU razdoblju od 1951. do 2023. godine analizirane su morfološke promjene triju žala: Plišivac, Minerva i Frara na području Makarskog primorja. Analize su temeljene na satelitskim (Google Earth) i ortofoto snimkama (DGU), a načinjene su u ArcGIS Pro i Agisoft softwareu. Analize su pokazale značajne promjene površina žala Plišivac tijekom posljednjih ~70-tak godina, u rasponu od 2 434,54 m2 do 3 958,83 m2 kod žala Plišivac, a od 452,32 m2 do 3 465,85 m2 kod žala Minerva. U istom razdoblju, žalo Frara bilježi samo manje promjene površine, od 825,08 m2 do 1181,1 m2. Razlog različite morfodinamike istraživanih žala je u značajnim antropogenim utjecajima na žalima Plišivac i Minerva gdje je došlo do višekratnih dohranjivanja žala, dok je žalo Frara nedostupno i potpuno prirodno. Osim faza naglog rasta površina žala, što možemo povezati s fazama dohranjivanja, analize pokazuju i epizode erozije koje su slijedile nakon dohranjivanja žala. Zbog dostupnosti velikog broja snimaka s poznatim datumom snimanja Google Earth snimke imale su najveći značaj u analizi promjena površine žala na istraživanom području.In the period from 1951 to 2023, the morphological changes of three beaches: Plišivac, Minerva and Frara were analysed in the Makarska littoral. The analyses are based on satellite (Google Earth) and orthophoto images (State Geodetic Administration) and were made in ArcGIS Pro and Agisoft software. The analyses have shown that the area of Plišivac beach has changed significantly in the last ~ 70 years, from 2,434.54 m2 to 3,958.83 m2 on Plišivac beach and from 452.32 m2 to 3,465.85 m2 on Minerva beach. In the same period, Frara beach showed only minor changes, from 825.08 m2 to 1181.1 m2. The reason for the different morphodynamics of the studied beaches is the significant anthropogenic influence on Plišivac and Minerva beaches, where there have been repeated nourishments, while Frara beach is inaccessible and completely natural. In addition to the phases of sudden growth of the beach surface, which we can associate with phases of nourishments, the analyses also show episodes of beach erosion that followed. Due to the availability of a large number of images with a known date of acquisition, the Google Earth records had the greatest importance in the analysis of morphological changes of beaches in the studied area
Novel imidazo[4,5-b]pyridine conjugates: synthesis, structural characterization and biological activity
No full textU okviru doktorskog rada opisana je sinteza, strukturna karakterizacija i biološka aktivnost novih derivata imidazo[4,5-b]piridina. Za sintezu novih spojeva korištene su klasične metode organske sinteze, sinteza potpomognuta mikrovalovima, paralelna sinteza i organometalna sinteza. Akrilonitrilni derivati 21–40 i 58–89 priređeni su aldolnom kondenzacijom 2-cijanometilimidazo[4,5-b]piridina s različitim benzaldehidima. Ispitan je utjecaj supstitucije u položaju N3 imidazo[4,5-b]piridinske jezgre, broj i položaj metoksi i hidroksi skupina, te prisutnost N,N-dialkilnog supstituenta u para-položaju fenilne jezgre na biološku aktivnost i spektroskopske karakteristike. Nadalje, reakcijom ciklokondenzacije
2-cijanometilimidazo[4,5-b]piridina i salicilbenzaldehida priređeni su iminokumarinski derivati 97–119 supstituirani u položajima 6 i 7 iminokumarinske jezgre, te na N3 dušikovom atomu imidazo[4,5-b]piridinske jezgre. 2-fenilamidino-supstituirani derivati imidazo[4,5-b]piridina 126–133 priređeni su iz cijano-supstituiranih prekursora 122–125, dok su reakcijom metiliranja priređeni derivati 134–136. Pinnerovom reakcijom u dva stupnja, priređeni su svi derivati supstituirani cikličkim amidinima, a one-pot reakcijom s reagensom LiHMDS derivati supstituirani nesupstituiranim amidinom. Suzukijevom reakcijom priređeni su derivati 142–146 i 149–154 supstituirani u položaju 6 imidazo[4,5-b]piridinske jezgre, a ovisno o korištenoj bornoj kiselini, u para-položaju fenilnog prstena supstituirani su različitim skupinama. N3-metil-supstituirani amidini imidazo[4,5-b]piridina 163–171 priređeni su iz cijano-supstituiranih prekursora 152, 161 i 162 Pinnerovom reakcijom. Serija konjugata imidazo[4,5-b]piridina i amidino-supstituiranih benzazola 182–190 priređena je kondenzacijom amidino-supstituiranih prekursora 173–181, odnosno
4-amidino-1,2-fenilendiamin-hidroklorida ili 5-amidino-2-aminobenzentiola s
imidazo[4,5-b]piridin-6-karbaldehidom 172. Schiffove baze imidazo[4,5-b]piridina 194–197 priređene su iz imidazo[4,5-b]piridina-karbaldehida 172 s anilinima, a Schiffove baze 202–214 iz 2-aminofenil-supstituiranih imidazo[4,5-b]piridina s benzaldehidima. Priređene su i dvije klase amidnih derivata imidazo[4,5-b]piridina koje se međusobno razlikuju prema položaju amidne veze. Derivati 217, 218, 230, 231 i 234 priređeni su iz benzoilnog klorida i amino-supstituiranih derivata, dok je derivat 222 priređen katalitički. Amidino-supstituirani derivati 219, 220, 232 i 233 priređeni su Pinnerovom reakcijom u dva stupnja.
Amino-supstituirani imidazo[4,5-b]piridini 102, 111, 147, 155, 233 i 235 priređeni su redukcijom iz odgovarajućih nitro-supstituiranih derivata. Radi bolje topljivosti derivati 103, 112, 119, 148, 156, 224 i 236 su pripravljeni kao amonijeve hidrokloridne soli. Strukture svih priređenih ciljanih spojeva i prekursora potvrđene su 1H i 13C NMR spektroskopijom, a za pojedine spojeve i dodatno masenom spektrometrijom. Detaljna spektroskopska karakterizacija u svrhu pronalaženja novih potencijalnih optičkih pH-senzora, provedena je za odabrane spojeve iz klasa akrilonitrila, iminokumarina i Schiffovih baza, a pKa vrijednosti određene su eksperimentalno i računalnim metodama. Svim ciljanim novopriređenim spojevima ispitana je antiproliferativna aktivnost in vitro na nekoliko staničnih linija humanih karcinoma. Za najaktivnije derivate istražen je mehanizam biološkog djelovanja koji je dodatno potvrđen, za neke derivate, i računalnom analizom. Antioksidativna aktivnost in vitro ispitana je spektroskopskim metodama DPPH, FRAP i ABTS, te elektrokemijski, dok je mehanizam antioksidativnog djelovanja potvrđen i računalnom analizom. Najaktivnijim amidinskim derivatima ispitana je interakcija s ct-DNK. Odabranim derivatima ispitana je antibakterijska aktivnost in vitro na nekoliko sojeva Gram-pozitivnih i Gram-negativnih bakterija, te antivirusna aktivnost in vitro prema odabranim vrstama virusa.Within this work, the synthesis, structural characterization and biological activity of novel imidazo[4,5-b]pyridine derivatives was described. For the synthesis of targeted compounds, classical methods of organic chemistry, parallel synthesis, and microwave assisted synthesis as well as organometal chemistry were used. Acrylonitrile derivatives 21–40 and 58–89 were prepared in the aldol condensation from 2-cyanomethylimidazo[4,5-b]pyridines and various benzaldehydes. Influence of N3 substitution on imidazo[4,5-b]pyridine core, the number and the position of hydroxy and methoxy groups as well as presence of N,N-dialkyl substituent placed at para-position of the phenyl ring on biological activity and spectroscopic characteristics was investigated. In the cyclocondensation reaction from 2-cyanomethylimidazo[4,5-b]pyridines and salicyl benzaldehydes, iminocoumarin derivatives 97–119 substituted at positions 6 and 7 of iminocoumarin core as well as at the position N3 of imidazo[4,5-b]pyridine nucleus were prepared. 2-phenylamidino-substituted
imidazo[4,5-b]pyridine derivatives 126–133 were prepared from cyano-substituted precursors 122–125, while derivatives 134–136 were prepared in the reaction of methylation. Two step Pinner reaction was used to prepare compounds substituted with cyclic amidines, while one pot reaction with LiHMDS was used to prepare derivatives with unsubstituted amidines. Suzuki coupling was used to prepare derivatives 142–146 and 149–154 substituted at the postition 6 of imidazo[4,5-b]pyridine core, depending on used boronic acid, substituted at the p–position of the phenyl ring with different substituents.
N3-methyl-substituted amidine derivatives 163–171 were prepared from cyano-substituted precursors 152, 161 and 162 in Pinner reaction and one pot reaction with LiHMDS. Benzazole conjugates of imidazo[4,5-b]pyridine with amidino-substituted benzazoles 182–190 were synthesized by condensation amidino-substituted precursors 173–181, respectively from 4-amidino-1,2-phenylenediamines hydrochlorides or 5-amidino-2-amino-substituted benzenthiolates with imidazo[4,5-b]pyridine-6-carbaldehyde 172. Imidazo[4,5-b]pyridine derived Schiff bases 194–197 were prepared from imidazo[4,5-b]pyridine-6-carbaldehyde 172 with various anilines, while Schiff bases 202–214 obtained from
2-aminophenyl-substituted imidazo[4,5-b]pyridines with benzaldehydes. Two series of amide derivatives were prepared which differ from position of amide bond. Derivatives 217, 218, 230, 231 and 234 were prepared by reactions between benzoil chlorides and
amino-substituted derivatives, while derivative 222 was prepared catalytically.
Amidino-substituted derivatives 219, 220, 232 and 233 were prepared by Pinner reaction.
All amino-substituted imidazo[4,5-b]pyridines 102, 111, 147, 155, 233 i 235 were prepared by reduction of corresponding nitro-substituted compounds. Some derivatives 103, 112, 119, 148, 156, 224 and 236 were prepared as ammonium hydrochloride salts in order to achieve better solubility. Structures of targeted compounds and precursors were analysed by means of 1H and 13C NMR spectroscopy, and were further confirmed by mass spectrometry for selected compounds. Thorough spectroscopic characterization was conducted for selected acrylonitrile, iminocoumarin and Schiff base derivatives, while pKa values were determined experimentally and computationally. All targeted compounds were evaluated for their antiproliferative activity in vitro on several human cancer cell lines. Mechanism of action was further investigated for the most active compounds and for some chosen derivatives confirmed also by computational analysis. Antioxidative activity in vitro was determined by using spectroscopic methods DPPH, FRAP and ABTS as well as electrochemically, while their mechanism of antioxidative action was explained by computational analysis. The most active amidine compounds were chosen for studying their interaction with ct-DNA. Selected compounds were tested also for their antibacterial activity in vitro against some Gram positive and Gram negative bacterial strains, as well as antiviral activity in vitro against selected viruses
Microbial degradation of xenobiotics under aerobic conditions
No full textMnoga znanstvena otkrića omogućila su bolju kvalitetu života i dovela do povećane proizvodnje ksenobiotika koji se najčešće nepravilno odlažu te su jedan od glavnih uzročnika loše kakvoće okoliša. Značajna skupina takvih tvari antropogenog podrijetla su farmaceutici. Kako oni imaju složenu strukturu i mehanizam djelovanja na različite vrste organizama, važno je pronaći nove i učinkovite načine uklanjanja ksenobiotika te pratiti njihov utjecaj na okoliš. U tu svrhu se sve više koriste ekonomični i okolišno prihvatljivi procesi poput biorazgradnje, koji koristi enzimske i metaboličke sposobnosti mikroorganizama za razgradnju organskih onečišćujućih tvari. U ovome radu proveden je proces biorazgradnje β-laktamskog antibiotika amoksicilina pomoću okolišne Gram-pozitivne bakterije Bacillus subtilis. Biorazgradnja amoksicilina provedena je u šaržnim i aerobnim uvjetima. Početne koncentracije amoksicilina iznosile su 278 mg L^-1 (Bs-1) i 658 mg L^-1 (Bs-2). Na temelju rezultata testova osjetljivosti, aktivnost bakterijske kulture Bacillus subtilis nije inhibirana djelovanjem navedenog antibiotika. Učinkovitost procesa biorazgradnje amoksicilina iznosila je 99,7 %.Many scientific discoveries have enabled a better quality of life and led to increased production of xenobiotics, most of which are improperly disposed of and are a major cause of poor environmental quality. An important group of such substances of anthropogenic origin are pharmaceuticals. Since they have a complex structure and mechanism of action on different types of organisms, it is important to find new and effective methods for disposing of xenobiotics and monitoring their impact on the environment. To this end, economical and environmentally sound methods such as biodegradation, which utilises the enzymatic and metabolic capabilities of microorganisms to degrade organic pollutants, are increasingly being used. In this work, the process of biodegradation of the β-lactam antibiotic amoxicillin was carried out using the environmentally occurring Gram-positive bacterium Bacillus subtilis. The biodegradation of amoxicillin was carried out in a batch process and under aerobic conditions. The initial concentrations of amoxicillin were 278 mg L^-1 (Bs-1) and 658 mg L^-1 (Bs-2). According to the results of the susceptibility tests, the activity of the Bacillus subtilis bacterial culture was not affected by the mentioned antibiotic. The efficiency of the biodegradation process of amoxicillin was 99.7 %
Oleotourism development potential in Istria County
No full textMaslinarski turizam novi je specifični oblik turizma koji se počinje razvijati u Istarskoj županiji. Bazira se na sudjelovanju posjetitelja u aktivnostima koje se temelje na valorizaciji maslinarske i uljarske baštine te uživanju maslinovog ulja i predstavlja način diversifikacije aktivnosti kojima se bave maslinarska poljoprivredna gospodarstva. Cilj ovog diplomskog rada bila je identifikacija jedinica lokalne samouprave Istarske županije s najvećim potencijalom razvoja maslinarskog turizma na temelju kvantitativne metodologije, i to kroz određivanje varijabli, odnosno statističkih pokazatelja, koje utječu na stupanj razvoja maslinarskog turizma, i izračun njihovih vrijednosti iz prikupljenih podataka. Velika količina podataka, odnosno oni koji se odnose na ponudu aktivnosti maslinarskog turizma, način njihove promidžbe te opremljenosti poljoprivrednih gospodarstava, prikupljeni su anketnim istraživanjem. Stupanj razvoja, predstavljen kroz izračunati kompozitni indeks, je kasnije stavljen u odnos s statističkim pokazateljima demografskog, prometnog, turističkog i maslinarskog razvoja provođenjem klaster analize koja je izdvojila pet različitih tipova područja u Istarskoj županiji ovisno o sedam izabranih varijabli.Oleotourism is a new specific type of tourism developing in the Istria County. It is based on the participation of visitors in activities that valorize olive farming and production, as well as olive heritage and the enjoyment of olive oil, and is a way of diversifying the activities of olive farms. The aim of this thesis was to identify the local self-government units of Istria County with the greatest potential for the development of oleotourism based on quantitative methodology, through the determination of variables, i.e. statistical indicators, which influence the level of development of oleotourism, and the calculation of their values from the collected data. A large amount of data, i.e. those related to the offer of olive tourism activities, the way of their promotion and the equipment of olive farms, were collected through survey research. The degree of development, presented through the calculated composite index, was later put into relation with statistical indicators of demographic, traffic, tourism and olive growing development by conducting a cluster analysis that distinguished five different types of areas in the Istria County based on seven selected variables
Degradation study of lipoglycodepsipeptide antibiotic ramoplanin by liquid chromatography and mass spectrometry
No full textU borbi protiv bakterijske rezistencije, ciklički lipoglikodepsipeptid ramoplanin pojavio se kao novi obećavajući antibiotski lijek. U ovom radu je razvijena, validirana i upotrjebljena metoda tekućinske kromatografije za praćenje stabilnosti ramoplanina, u čvrstom stanju i u otopini. Studija forsirane razgradnje provedena je podvrgavanjem uzorka različitim stresnim uvjetima (kisela i bazična hidroliza, oksidacija, vlaga, temperatura i svjetlo) te su opaženi razgradni produkti razjašnjeni spektrometrijom masa. Istraživanje je otkrilo kako je hidroliza laktonskog prstena najvažniji degradacijski put molekule. Međutim, opaženi su i drugi značajni putevi degradacije. Nadalje, ramoplanin je formuliran u vodenim otopinama koristeći nekoliko različitih pomoćnih tvari te je provedena stabilitetna studija pri 25 °C/60 % RV i 40 °C/75 % RV. Među ispitanim pomoćnim tvarima, polisorbat 20, Kolliphor® RH 40 i kolin klorid pokazali su važan stabilizacijski učinak na degradaciju ramoplanina.In the fight against antimicrobial resistance, a cyclic lipoglycodepsipeptide ramoplanin emerged as a new promising antibacterial regimen. In the present work, an LC method was developed, validated and used during stability testing of ramoplanin, in solid state and in solution. Forced degradation study was performed by subjecting the sample to different stress conditions (acid and base hydrolysis, oxidation, humidity, heat and light) and the observed degradation products were elucidated using mass spectrometry. The study revealed that the most significant degradation path of the molecule is hydrolysis of its lactone ring. However, other significant degradation routs were also observed. Furthermore, ramoplanin was formulated in aqueous solutions using several different excipients and a stability study was conducted at 25 °C/60 % RH and 40 °C/75 % RH. Among the tested excipients, polysorbate 20, Kolliphor® RH 40 and choline chloride were found to have an important stabilizing effect on the degradation of ramoplanin