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Realease kinetics of antitumor drug from composite microcarriers
No full textLjudsko tkivo nema mehanizam obrane od stanica raka i njihovih brzih replikacija. Jedan od primarnih načina suzbijanja takve zloćudne abnormalnosti je izravno uklanjanje nastalog tkiva raka, primjena kemoterapije (antitumorskih lijekova) ili zračenje. Doksorubicin (DOX), kemoterapijski lijek, a i njegovi bioaktivni derivati su među najraširenijim lijekovima za takve tretmane. Razvoj manje invazivnih, „pametnih“ materijala, poput sustava za dostavu lijekova, nastao je iz potrebe za naprednim postupcima liječenja tumora. Isporuka lijeka sa ciljanom dostavom osigurava lokalizirano liječenje tumorskog tkiva, minimizirajući izloženost cijelog tijela. Kitozan (CHT) je poznat po svojoj biokompatibilnosti, hidrofilnosti, netoksičnosti i biorazgradljivosti. Štoviše, kitozan ima polikationsku prirodu zbog prisutnih amino skupina, što omogućuje oslobađanje lijeka iz polimernih matrica ovisno o pH vrijednosti medija te osigurava unutarstaničnu dostavu antitumorskih lijekova. U ovom radu istražen je utjecaj različitih inkubacijskih medija na profil otpuštanja antitumorskog lijeka (doksorubicina) iz pripremljenih kompozitnih materijala na temelju hidroksiapatita i kitozana fizikalno umreženog bakrovim(II) ionima (CHT-Cu/CaP), primjenom fluorescentne spektrofotometrije. Otpuštanje DOX-a iz mikročestica različitog kemijskog sastava (0, 5 i 10 mas.% CaP-a) praćeno je tijekom 72 h u fosfatnom puferu pH vrijednosti 6 (PB-6) i 7,4 (PB-7,4) te u mediju za staničnu kulturu (CCM). Dobiveni rezultati ukazuju na veće otpuštanje lijeka iz mikročestica s najvećim udjelom anorganske faze (CHT-Cu/CaP10), a najmanja količina DOX-a je otpuštena iz mikročestica bez dodatka CaP-a (CHT-Cu/CaP0). Medij u kojem je otpuštena najveća količina doksorubicina je medij za staničnu kulturu (CCM), a prati ga PB-6 pa PB-7,4. Takvi rezultati se pripisuju stabilnosti mikronosača zbog stabilnost kalcij-fosfata i ograničene topljivosti kitozana pri fiziološkim uvjetima. Dobiveni rezultati ukazuju na to da kemijski sastav mikronosača, kao sastav i pH inkubacijskog medija, utječu na profil otpuštanja lijeka, te da CHT-Cu/CaP mikročestice imaju veliki potencijal za upotrebu kao dostavljači doksorubicina za ciljanu isporuku lijeka pri liječenju raka kosti.Human tissue lacks a defense mechanism against cancer cells and their rapid replication. One of the primary ways to combat such malignant abnormalities is through direct removal of the resulting cancer tissue, application of chemotherapy (antitumor drugs), or radiation. Doxorubicin (DOX), a chemotherapeutic drug, and its bioactive derivatives are among the most widespread drugs for such treatments. The development of less invasive, “smart” materials, such as drug delivery systems, arose from the need for advanced tumor treatment methods. Targeted drug delivery ensures localized treatment of tumor tissue, minimizing exposure to the entire body. Chitosan (CHT) is known for its biocompatibility, hydrophilicity, non-toxicity, and biodegradability. Moreover, chitosan has a polycationic nature due to the presence of amino groups, which allows drug release from polymeric matrices depending on the pH value of the medium, ensuring intracellular delivery of antitumor drugs. This study investigates the impact of different incubation media on the release profile of the antitumor drug (doxorubicin) from prepared composite materials based on hydroxyapatite and chitosan physically cross-linked with copper (II) ions (CHT-Cu/CaP), using fluorescence spectrophotometry. The release of DOX from microparticles of different chemical compositions (0, 5, and 10 wt.% CaP) was monitored over 72 hours in phosphate buffer solution at pH 6 (PB-6) and 7.4 (PB-7.4), as well as in cell culture medium (CCM). The results indicate greater drug release from microparticles with the highest amount of the inorganic phase (CHT-Cu/CaP10), while the smallest amount of DOX was released from microparticles without CaP (CHT-Cu/CaP0). The medium in which the largest amount of doxorubicin was released is cell culture medium (CCM), followed by PB-6 and then PB-7,4. Such results are attributed to the stability of the microcarriers due to the stability of calcium phosphate and limited solubility of chitosan under physiological conditions. The obtained results indicate that the chemical composition of microcarriers, as well as composition and pH value of the incubation medium influence the drug release profile, and suggest that CHT-Cu/CaP microcarriers have immense potential for use as doxorubicin delivery systems for targeted drug delivery in bone cancer treatment
Development and validation of the HPLC-DAD method for thedetermination of a mixture of selected xenobiotics
No full textKsenobiotici u okolišu završavaju najvećim djelom zbog antropološkog djelovanja i to osobito zbog neučinkovite obrade otpadnih voda iz industrijskih postrojenja. Praćenje ksenobiotika moguće je jedino analitičkim metodama, a jedna od najučinkovitijih je tekućinska kromatografija visoke učinkovitosti s detektorom s nizom dioda (HPLC-DAD). Da bi bilo moguće određivati ksenobiotike različitih fizikalno-kemijskih svojstava istovremeno nužno je izabrati odgovarajuću nepokretnu i pokretnu fazu za kromatografsku separaciju izabranih ksenobiotika. Nakon razvoja metode i odabira kromatografskih uvjeta metodu je nužno validirati. To podrazumijeva određivanje niza validacijskih parametara. Dakle, glavni ciljevi ovog rada su razvoj kromatografske metode i određivanje validacijskih parametara
HPLC-DAD metode te potvrditi njenu primjenu za analizu izabranih ksenobiotika u uzorcima.Xenobiotics in the environment mostly end up thanks to anthropological action, especially due to inefficient treatment of waste water from industrial plants. Monitoring of xenobiotics is only possible with analytical methods, and one of the most effective is highperformance liquid chromatography with a diode array detector (HPLC-DAD). In order to be able to determine xenobiotics with different physico-chemical properties at the same time, it is necessary to choose an appropriate stationary and mobile phase for the chromatographic separation of the selected xenobiotics. After developing the method and choosing the chromatographic conditions, it is necessary to validate the method. This implies the determination of a number of validation parameters. Therefore, the main goals of this work are the development of the chromatographic method and the determination of the validation parameters of the
HPLC-DAD method and to confirm its application for the analysis of selected xenobiotics in samples
Bioremediation of wastewater from the coke industry
No full textKoksna industrija pripada u skupinu industrija koje u velikim razmjerima onečišćuju okoliš. Zbog svog izrazito složenog sastava i širokog raspona varijacija komponenata, obrada otpadnih koksnih voda nije jednostavna. Niti jedan proces obrade ne može se provesti samostalno, a da rezultira zadovoljavajućim stupnjem pročišćenosti. Zbog toga se uvijek koriste kombinirani postupci, započevši od fizikalno-kemijske obrade, do biološke, na koju se danas sve više istraživanja okreće zbog svog velikog stupnja isplativosti. Bioremedijacija temeljena na mikroorganizmima je održiva obrada s dobrom izvedbom, niskim troškovima održavanja i izvrsnom selektivnošću. Odabir odgovarajućih sojeva mikroorganizama ključan je u bioremedijaciji, te s dostupnim širokim rasponom algi, gljiva i bakterija proces se može prilagoditi koksnim vodama različitih svojstava. U ovom radu biti će dan način nastanka otpadnih koksnih voda, popis njihovih svojstava, kao i glavnih onečišćujućih tvari koje su u njima prisutne. Opisati će se načini obrade koksnih voda s naglaskom na biološki način obrade, pri čemu će biti poseban osvrt na bioremedijaciju gljivama, bakterijama i algama.The coke industry belongs to the group of industries that pollute the environment on a large scale. Due to its extremely complex composition and wide range of component variations, the treatment of waste coke water is not simple. No treatment process can be carried out independently without resulting in a satisfactory degree of purification. For this reason, combined procedures are always used, starting from physio-chemical processing, to biological, to which more and more research is turning today due to its high degree of profitability. Microorganism-based bioremediation is a sustainable treatment with good performance, low maintenance costs and excellent selectivity. The selection of appropriate strains of microorganisms is crucial in bioremediation, and with a wide range of algae, fungi and bacteria available, the process can be adapted to coking waters of different properties. This paper will present the method of generation of waste coke water, a list of their properties, as well as the main pollutants present in them. Methods of coke water treatment will be described with an emphasis on biological treatment method, with a special focus on bioremediation with fungi, bacteria and algae
Self-assembly of fatty acids on copper from a mixture of different acids for the purpose of corrosion protection
No full textU današnje vrijeme mnogi novi materijali svakodnevno dolaze na tržište. Potraga za novim materijalima ili poboljšanje svojstava starih materijala je od velike važnosti zbog promjena koje se događaju u atmosferi uslijed globalnog zatopljenja i sve većih zahtjeva za korištenim materijalima. Zbog povećanog zagađenja okoliša, trošenje ili degradacija sveprisutnih konstrukcijskih materijala, posebice metala, sve je češća pojava. U ovom radu istraživana su svojstva prevlaka pripremljenih od masnih kiselina samoorganiziranih na površinu bakra te umreženih ionizirajućim zračenjem. Samoorganizirane prevlake masnih kiselina pružaju određenu kratkotrajnu zaštitu bakru u atmosferskim uvjetima, dok njihovim umrežavanjem pomoću ionizirajućeg zračenja, svojstva prevlaka postaju značajno bolja, stabilnija i dugotrajnija. Cilj istraživanja bio je ispitati mogućnost nastajanja umreženih prevlaka samoorganizirajućih masnih kiselina iz mješavine zasićenih masnih kiselina različitih duljina lanaca (od 6, 18 i 22 ugljikova atoma). Zaštitna svojstva nastalih prevlaka uspoređivane su sa svojstvima prevlaka nastalim iz pojedinačnih ispitivanih masnih kiselina. Svojstva prevlaka ispitivana su termogravimetrijskom analizom, mjerenjem kontaktnog kuta i elektrokemijskim metodama.Nowadays, many new materials are entering the market every day. Searching for new materials or changing the properties of old materials is of great importance because of the changes occurring in the atmosphere due to global warming and the increasing demands on the materials used. Due to increasing environmental pollution, wear or degradation of ubiquitous construction materials, especially metals, is becoming more common. In this work, the properties of coatings, prepared by self-assembly of fatty acids on the surface of copper and their crosslinking by ionizing radiation, were investigated. Crosslinking with ionizing radiation makes the properties of the coatings significantly better, more stable and durable. The aim of the research was to investigate the possibility of producing a coating of crosslinked self-assembled fatty acids from a mixture of saturated fatty acids with different chain lengths (6, 18 and 22 carbon atoms). The protective properties of the resulting coatings were compared with the coatings made from individual studied fatty acids. The properties of the coatings were investigated using thermogravimetric analysis, contact angle measurements, and electrochemical methods
Synthesis and structural characterization of 1,2-disubstituted benzimidazole derivatives
No full textU ovom radu opisana je sinteza novih derivata benzimidazola supstituiranih u položaju 1 triazolnim supstituentima i u položaju 2 arilnim supstituentima (9-16). U prvom stupnju sinteze su pripravljeni kao ključni prekursori arilbenzimidazoli 1 i 2 reakcijom ciklizacije odgovarajućih 1,2-diaminobenzena i benzaldehida koji su potom u sljedećem stupnju reakcije alkiliranja prevedeni u N-propargilirane derivate benzimidazola 3 i 4. U zadnjem stupnju je Huisgenovom 1,3-dipolarnom cikloadicijom propargiliranih derivata benzimidazola (3 i 4) s odgovarajućim priređenim azidima (5-8), uz Cu(Ac)2 kao katalizator; u položaj
N-1 benzimidazola uveden 1,2,3-triazolni prsten. Strukture svih novopripravljenih derivata benzimidazola potvrđene su spektroskopijom 1H i 13C-NMR.This paper describes the synthesis of new benzimidazole derivatives substituted in position 1 with triazole substituents and in position 2 with aryl substituents, (9-16). In the first stage of synthesis, arylbenzimidazoles were prepared as key precursors 1 and 2 by the cyclization reaction of the corresponding 1,2-diaminobenzene and benzaldehyde, which were then converted into N-propargylated derivates of benzimidazole 3 and 4 in the next stage of the alkylation reaction. In the last stage, through Huisgen 1,3-dipolar cycloaddition of propargylated benzimidazole derivatives (3 and 4) with the corresponding prepared azides (5-8), using Cu(Ac)2 as a catalyst, a 1,2,3-triazole ring was introduced at the N-1 position of benzimidazole. The structures of all newly synthesized benzimidazole derivatives were confirmed by spectroscopy 1H and 13C-NMR
Structure and properties of PEG/n-ZnO nanocomposite
No full textU ovom radu istražena su svojstva PEG12000 i PEG20000 polimera i PEG/n-ZnO kompozita s različitim udjelom nanočestica. PEG koji ima vrlo dobru biokompatibilnost i hidrofilna svojstvima, odabran je kao polimerna matrica, dok je nano ZnO, zahvaljujući svojim antibakterijskim svojstvima i svojstvima apsorpcije UV zračenja, odabran je kao punilo. Kompoziti su pripravljeni u vodenoj otopini zamiješavanjem nano-ZnO čestica s PEG polimerom. Svojstva PEG polimera i PEG/n-ZnO kompozita različitog sastava istražena su primjenom različitih tehnika. Površinske karakteristike određene su mjerenjem kontaktnog kuta na goniometru. Toplinska svojstva istražena su primjenom diferencijalne pretražne kalorimetrije i termogravimetrijske analize. Istražena su svojstva PEG i PEG/n-ZnO nakon ubrzanog starenja djelovanjem UV zračenja u vremenu od 24 sati i 120 sati. Strukturne promjene nakon UV zračenja praćene su primjenom FTIR (Fourier-transform infracrvena spektroskopija) analize. Rezultati su pokazali da se na međupovršini PEG20000/n-ZnO uspostavljaju slabije interakcije u odnosu na PEG12000/n-ZnO. Kompoziti s većim udjelom nanočestica razrušavaju kristalnu strukturu PEG polimera i ne doprinose povećanju na toplinske stabilnosti. Bolja zaštitna svojstva od UV zračenja pokazao je sustav s PEG12000 i većim udjelom n-ZnO punila.In this study, the properties of PEG12000 and PEG20000 polymers and of PEG/n-ZnO composites with different nanoparticle contents were investigated. PEG, which has very good biocompatibility and hydrophilic properties, was chosen as the polymer matrix, while
nano-ZnO was selected as the filler due to its antibacterial and UV absorption properties.
The composites were prepared in aqueous solution by mixing nano-ZnO particles with PEG polymers. The properties of the PEG polymers and the PEG/n-ZnO composites of different compositions were investigated using different techniques. The surface properties were determined by measuring the contact angle with a goniometer. The thermal properties were investigated by differential scanning calorimetry and thermogravimetric analysis.
The properties of PEG and PEG/n-ZnO were investigated after accelerated aging by
UV irradiation over 24 hours and 120 hours. Structural changes after UV irradiation were monitored by FTIR (Fourier transform infrared spectroscopy) analysis. The results showed that weaker interactions occur at the PEG20000/n-ZnO interface compared to PEG12000/n-ZnO. Composites with a higher content of nanoparticles disable the crystalline structure of the PEG polymer and do not contribute to an increase in thermal stability. The system with PEG12000 and a higher content of n-ZnO filler showed better protective properties against UV radiation
Plan upravljanja istraživačkim podacima projekta Pametni sustavi za dostavu lijeka pri liječenju tumora kosti (UIP-2020-02-6201)
No full textFormulation of nutshell and geopolymer biocomposites
No full textModerna istraživanja materijala vođena su pravilima održivog razvoja, što obuhvaća racionalnu uporabu resursa i zaštitu okoliša kroz smanjenje potrošnje energije, generiranog otpada i emisije stakleničkih plinova. Cilj je razvoj naprednih materijala koji će biti dobiveni oporabom otpadnih materijala ili korištenjem materijala s minimalnim ekološkim otiskom. Primjer otpadnog materijala s mogućnošću oporabe su otpadne ljuske orašastih plodova koje se najčešće zbrinjavaju paljenjem, tj. koriste se kao gorivo. S druge strane, geopolimerni sustavi se razvijaju kao zamjena za obični portland cement zbog znatno manjeg ekološkog otiska. U ovome radu ispitana je mogućnost pripreme naprednog biokompozita kao izolacijskog materijala korištenjem otpadnih ljuski badema i lješnjaka kao čestičnog punila te geopolimernog veziva kao matrice. Proučavan je utjecaj dva načina predobrade otpadne ljuske na svojstva ljuski i njihovih biokompozita. Predobrada otopinom NaOH, tj. mercerizacija provedena je s 3, 6, i 9 mas.% otopinom u trajanju od 1 i 2,5 h pri 80 °C. Ljuske su obrađene vapnenim mlijekom koncentracije 12,5 mas.% pri 80 °C tijekom 1 i 2,5 h te na sobnoj temperaturi 24 h. Geopolimerna veziva pripremljena su korištenjem metakaolina i lebdećeg pepela kao čvrstih prekursora te kombinacije natrijevih/kalijevih hidroksida i vodenih stakala kao aktivacijskih otopina. Rendgenskom difrakcijskom analizom ljuske utvrđen je porast indeksa kristaličnosti (CI) sa načinom predobrade, iako bez jasnog trenda, što je povoljno za korištenje ljuske u biokompozitima s anorganskom matricom. Veći CI ukazuje na uklanjanje amorfnih doprinosa u strukturi koji upijaju velike količine vode i time utječu na svojstva biokompozita. Usto veća kristaličnost omogućuje bolju adheziju između anorganske matrice i ove vrste materijala. Nadalje, infracrvenom spektroskopijom s Fourierovom transformacijom (FTIR) i simultanom diferencijalnom toplinskom i termogravimetrijskom analizom (DTA/TGA) dokazano je uspješno uklanjanje nepoželjnih sastavnica ljuske, točnije lignina, hemiceluloze i različitih ekstraktiva. Povećanjem vremena tretmana i koncentracije otopine za predobradu poboljšava se uklanjanje nepoželjnih sastavnica, dok je predobrada vapnenim mlijekom manje efikasna od mercerizacije. Određivanje površinskih svojstava i parametara adhezije mjerenjem kontaktnog kuta provedeno je na svim uzorcima ljuske i geopolimera. Kroz njihove vrijednosti moguće je pokušati predvidjeti optimalnu predobrade za određene vrste geopolimera. Tako predobrada otopinom 6 mas.% NaOH na 80 °C i 2,5 h za ljusku lješnjaka tvori biokompozite s najboljim svojstvima sa svim vrstama geopolimera, dok je u slučaju ljuske badema optimalna predobrada 9 mas.% otopinom NaOH na 80 °C i 2,5 h u kombinaciji s geopolimerom dobivenim iz lebdećeg pepela aktiviranog natrijevim otopinama. Mjerenjem tlačnih čvrstoća kao glavnog parametra uspješnosti predobrade i vrste biokompozita određeno je kako je optimalni maseni omjer geopolimera i ljuske 2 te kako su sobni uvjeti najbolji za pripremu biokompozita. Ispitivanjem vrste čvrstog prekursora zaključeno je da će se za pripremu biokompozita koristiti metakaolin, jer njegovi biokompoziti imaju do 160% veće tlačne čvrstoće od onih pripremljenih iz lebdećeg pepela. Također, odabrane su kalijeve otopine zbog 53 i
22 % većih tlačnih čvrstoća biokompozita ljuski badema i lješnjaka u odnosu na natrijeve aktivacijske otopine otopine. Parametri adhezije za obje vrste ljuske predviđaju mercerizaciju sa 6 mas.% na 80 °C i 2,5 h kao optimalni način predobrade. Unatoč tim predviđanjima, obrada vapnenim mlijekom ipak daje veće čvrstoće što se može povezati s nastankom kalcijevih amorfnih faza unutar geopolimera koje doprinose povećanju čvrstoća. Savojne čvrstoće nisu dale pouzdane rezultate, što je posljedica vrste materijala i male osjetljivosti kidalice. Toplinska svojstva, tj. izmjerene toplinske provodnosti upućuju na dobra izolacijska svojstva ove vrste biokompozita. Na temelju rezultata dobivenih u ovom istraživanju može se zaključiti kako je moguće pripraviti biokompozite iz ljuski badema i lješnjaka te geopolimera koji zadovoljavaju očekivanja u pogledu svojstava te su u skladu s principima održivog razvoja, čime se otvara prostor za daljnji razvoj ekološki prihvatljivih i funkcionalnih materijala s minimalnim ekološkim otiskom.Modern materials research is guided by the principles of sustainable development, which include the rational use of resources and environmental protection through reduced energy consumption, waste generation and greenhouse gas emissions. The goal is to develop advanced materials derived from the recycling of various waste materials or from materials with a minimal ecological footprint. An example of recyclable waste materials is nut shells, which are most often disposed of by incineration, i.e. used as fuel. On the other hand, geopolymer systems are being developed as a replacement for ordinary Portland cement due to their significantly smaller ecological footprint. In this work, the feasibility of preparing an advanced biocomposite as an insulating material using waste almond and hazelnut shells as particulate fillers and a geopolymer binder as the matrix was examined. The influence of two methods of waste shell pretreatment on the properties of the shells and their biocomposites was studied. Pretreatment with NaOH solution, i.e. mercerization was carried out with 3, 6, and 9 wt.% solution for 1 and 2.5 h at 80 °C. Milk of lime with a concentration of 12.5 wt.% was prepared by mixing Ca(OH)2 and demineralized water, and the shells were treated at
80 °C for 1 and 2.5 h and at room temperature for 24 h. Geopolymer binders were prepared using metakaolin and fly ash as solid precursors and a combination of sodium/potassium hydroxides and water glasses as activation solutions. X-ray diffraction analysis of the shells revealed an increase in the crystallinity index (CI) with the pretreatment method, although without a clear trend, which is favorable for the use of the shells in biocomposites with an inorganic matrix due to better adhesion with the rise of CI. Furthermore, rise of CI indicates the removal of unwanted amorphous phases that readly absorb water, which impairs mechanical properties of their biocomposites. Additionaly, Fourier transform infrared spectroscopy and simultaneous differential thermal and thermogravimetric analysis demonstrated the successful removal of undesirable shell components, namely lignin, hemicellulose and various extractives. Increasing the time and concentration of the pretreatment solution improves the removal of undesirable components, while pretreatment with milk of lime is less efficient than mercerization. Determination of surface properties and adhesion parameters by measuring the contact angle was carried out on all shell and geopolymer samples. Through this analysis, it was predicted that the pretreatment with a 6 wt.% NaOH solution at 80 °C and 2.5 h for hazelnut shell should result in biocomposites with the best properties with all types of geopolymers matrices, while in the case of almond shell, the optimal pretreatment is with a
9 wt.% NaOH solution at 80 °C and 2.5 h in combination with a geopolymer obtained from fly ash activated with sodium solutions. By measuring compressive strengths as the primary indicator of pretreatment and biocomposite performance, it was determined that the optimal mass ratio of geopolymer to shell is 2 and that room conditions are the best for the preparation of biocomposites. Through the analysis of the type of solid precursor it was concluded that metakaolin will be used for preparation of biocomposites and for testing the influence of pretreatment as their compressive strength value is up to 160 % higher than those made with fly ash. Likewise, potassium solutions were chosen due to the 53% and 22% higher compressive strengths of almond and hazelnut shell biocomposites compared to sodium activation solutions. For both types of shells, in the case of mercerization, the optimal processing conditions are a concentration of 6 wt.% at 80 °C and 2.5 h, which is also predicted by the adhesion parameters. Despite these predictions, treatment with milk of lime results in higher strengths, which can be associated with the formation of calcium amorphous phases within the geopolymers that contribute to enhanced strength. Flexural strengths did not give reliable results, which is a consequence of the type of material and the low sensitivity of the testing apparatus. Thermal properties, i.e. measured thermal conductivities, indicate good insulating properties of this type of biocomposites. Based on the results obtained in this research, it can be concluded that it is possible to prepare biocomposites from waste almond and hazelnut shells and geopolymers that meet expectations in terms of properties, while adhering to the principles of sustainable development. This paves the way for the further development of environmentally friendly and functional materials with a minimal ecological footprint
Synthesis and spectroscopic characterization of coumarin and pyridine conjugates and their metal complexes
No full textKumarinski derivati imaju brojnu primjenu u medicini kao spojevi s antikoagulacijskim, antimikrobnim, antikancerogenim, antioksidativnim te antivirusnim djelovanjem. Cilj ovog rada bila je sinteza potencijalno biološki aktivnih konjugata kumarina i piridina te njihovih metalnih kompleksa. U tu su svrhu pripravljeni azidni kumarinski prekursori 1-6 dvostupanjskom sintezom primjenom reakcije Pechmannove ciklizacije i reakcijom supstitucije, dok su O-propargilirani eteri kumarina 7 i 8 dobiveni jednostupanjskom sintezom primjenom reakcije O-alkiliranja. Navedeni spojevi su korišteni u klik reakciji Huisgenove 1,3-dipolarne cikloadicije katalizirane bakrom(I) kako bi se pripravili spojevi 11-18 s 1,2,3-triazolnom premosnicom između kumarinske jezgre i piridinskog prstena. Konjugati kumarina i piridina korišteni su, kao ligandi, u sintezi kompleksa s Ru(II) 19-26. Strukture dobivenih kumarinskih derivata i njihovih kompleksa potvrđene su spektroskopijom 1H i 13C NMR, IR i UV/Vis. Kristalna struktura kompleksa 24 određena je difrakcijom X-zraka u jediničnom kristalu. Antiproliferativno djelovanje ispitano je na staničnim linijama karcinoma jetre (HepG2), dojke (MCF7), gušterače (PANC1), debelog crijeva (RKO) te normalnoj staničnoj liniji (HEK293).Coumarin derivatives are widely used in medicine as compounds with anticoagulant, antimicrobial, anticancer, antioxidant and antiviral effects. The aim of this work was the synthesis of potentially biologically active conjugates of coumarin and pyridine and their metal complexes. For this purpose azide coumarin precursors 1-6 were prepared by two step synthesis using Pechmann cyclization reaction and substitution reaction, while the terminal alkynes O-propargylated ethers 7 and 8 were prepared by one step- O-alkylation reaction. These compounds were used in a copper(I) catalyzed Husigen 1,3-dipolar cycloaddition click reaction to prepare compounds 11-18 with a 1,2,3-triazole bridge between the coumarin core and the pyridine ring. Coumarin and pyridine conjugates were used as ligands in the synthesis of complexes 19-26 with Ru(II). The structures of the obtained coumarin derivatives and their complexes were confirmed by 1H and 13C NMR, IR and UV/VIS spectroscopy. The crystal structure of complex 24 was determined by single-crystal X-ray diffraction. Antiproliferative activity was evaluated on liver (HepG2), breast (MCF7), pancreatic (PANC1), colon (RKO) and normal cell lines (HEK293)
The novel benzoxazole derivatives: synthesis and structural characterization
No full textU ovom radu opisana je sinteza novih derivata benzoksazola i njihova strukturna karakterizacija 1H- i 13C-NMR spektroskopijom. Reakcijom 4-hidroksibenzaldehida i odgovarajućih alkilirajućih reagenasa pripravljeni su O-alkilirani benzaldehidi (1-6) kao prekurosri koji su zatim s različito supstituiranim ortho-aminofenolima prevedeni u derivate Schiffovih baza (7-19). Oksidativnom ciklizacijom Schiffovih baza sintetizirani su derivati benzoksazola (20-32). Mikrovalno potpomognutim O-propargiliranjem
4-(5-metoksibenzo[d]oksazol-2-il)fenola (32) s propargil-bromidom uz kalijev karbonat kao bazu sintetiziran je 5-metoksi-2-(4-(prop-2-in-1-iloksi)fenil)benzo[d]oksazol (33) koji je potom klik reakcijom 1,3-dipolarne cikloadicije katalizirane bakrovim(I) jodidom s prethodno dobivenim azidima (34-36) preveden u 1,2,3-triazolne derivate benzoksazola (37-39). Strukture svih novopripravljenih derivata benzoksazola potvrđene su 1H- i 13C-NMR spektroskopijom.This work describes the synthesis of new benzoxazole derivatives and their structural characterization by 1H- and 13C-NMR spectroscopy. The reaction of 4-hydroxybenzaldehyde and the corresponding alkylating reagents prepared O-alkylated benzaldehydes (1-6) as precursors which were then converted into derivatives of Schiff bases (7-19) with variously substituted ortho-aminophenols. Oxidative cyclization of Schiff bases benzoxazole derivatives (20-32) were synthesized. Microwave-assisted O-propargylation of 4-(5-methoxybenzo[d] oxazol-2-yl)phenol (32) with propargyl bromide using potassium carbonate as a base synthesized 5-methoxy-2-(4-(prop-2)-in-1-yloxy)phenyl)benzo[d]oxazole (33) which was then converted to 1,2,3-triazole benzoxazole derivatives (37-39) by the click reaction of
1,3-dipolar cycloaddition catalyzed by copper (I) iodide with previously obtained azides (34-36). The structures of all newly prepared benzoxazole derivatives were confirmed by
1H- and 13C-NMR spectroscopy