University of Zagreb
Repository of Faculty of Pharmacy and Biochemistry University of ZgrebNot a member yet
2946 research outputs found
Sort by
Synthesis, characterization and derivatization of a polysubstituted piperidino-morpholine spiro building block
No full textMale molekule s novim mehanizmima djelovanja neophodne su u rješavanju izazovnih biomedicinskih problema današnjice poput rezistencije na postojeće lijekove za liječenje raka i zaraznih bolesti. Jedan od pristupa otkriću novih biološki aktivnih molekula uključuje sintezu usmjerenu na raznolikost (engl. diversity-oriented synthesis, DOS), koja primarno podrazumijeva razlike u strukturnoj okosnici, supstituentima i stereokemiji. Različiti lijekovi koji u svojoj strukturi sadrže morfolinski prsten imaju široku terapijsku primjenu. Privilegirani je farmakofor s mogućnošću stvaranja molekulskih interakcija s raznovrsnim biološkim metama i modificiranja farmakokinetičkih svojstava. Stoga je morfolin strukturni motiv od posebnog interesa za dizajniranje i razvoj lijekova. Istodobno je povećan interes za sintezu manje planarnih biološki aktivnih spojeva što rezultira uvođenjem spiro spojeva u nova istraživanja.
Slijedom navedenih spoznaja, cilj ovog diplomskog rada bila je sinteza i karakterizacija polisupstituiranog piperidino-morfolinskog spiro gradivnog bloka te njegova derivatizacija u svrhu dobivanja novih spojeva s različitim svojstvima, korištenjem principa sinteze usmjerene na raznolikost. Osnovna strukturna okosnica sintetizirana je preko dva sintetska puta, u šest odnosno četiri reakcijska koraka, od kojih je zadnji korak intramolekulska ciklizacija u bazičnim uvjetima. U nekoliko sljedećih sintetskih koraka, iz glavnog intermedijara 6, pripravljeni su odgovarajući prekursori. Šest novih derivata 9a-c i 13a-c dobiveno je iz spojeva 8 i 12 s dvije slobodne amino-skupine, završnim reakcijama N-acetiliranja, sulfonamidacije i Eschweiler-Clarke reakcijom. Strukturna raznolikost postignuta je supstituiranjem osnovne strukturne okosnice u tri različita položaja, a strukture novosintetiziranih spojeva potvrđene su uobičajenim spektroskopskim metodama (1D i 2D NMR, MS). Dokazana je izražena trodimenzionalnost struktura finalnih spojeva 9a-c i 13a-c pomoću NOESY NMR spektara. Finalnim spojevima određena su i fizikalno-kemijska svojstva in silico.Small molecules with novel mechanisms of action are necessary in addressing today’s challenging biomedical problems such as resistance to existing drugs for the treatment of cancer and infectious diseases. One of the approaches to the discovery of new bioactive molecules includes diversity-oriented synthesis (DOS), which primarily implies differences in the molecular scaffold, substituents and stereochemistry. Various drugs containing a morpholine ring in their structure are widely used for the treatment of numerous diseases. It is a privileged pharmacophore with the possibility of forming molecular interactions with diverse biological targets and modifying pharmacokinetic properties. Therefore, morpholine is a structural motif of special interest for the drug design and development. At the same time, interest for the synthesis of less planar bioactive compounds increases, resulting in the introduction of spiro compounds into new studies.
Following the stated facts, the aim of this thesis was to synthesize and characterize polysubstituted piperidino-morpholine spiro building block. Furthermore, this scaffold was derivatized in order to obtain novel compounds with different properties, using the diversity-oriented synthesis approach. The scaffold was synthesized via two synthetic routes, in six or four reaction steps, with the last step of intramolecular cyclization under basic conditions. In several subsequent chemical reactions, the corresponding precursors were prepared from the main intermediate 6. Six novel derivatives 9a-c and 13a-c were obtained from compounds 8 and 12 with two free amino groups by N-acetylation, sulfonamidation and Eschweiler-Clarke reaction respectively. Structural diversity was achieved by substituting the scaffold at three different positions. The structures of the novel compounds were confirmed by standard spectroscopic methods (1D and 2D NMR, MS). Noticeable three-dimensionality of the structures of the final compounds 9a-c and 13a-c was proved by means of NOESY NMR spectra. Additionally, the physicochemical properties of final compounds were calculated in silico
Determination of metals in dietary supplements for the treatment of inflammatory bowel diseases using atomic absorption spectrometry
No full textBroj oboljelih od upalnih bolesti crijeva u stalnom je porastu. Ovi pacijenti često koriste različite dodatke prehrani kao potporu samoj terapiji lijekovima. Dodaci prehrani koji sadrže biljne vrste poput kurkume, justicije i indijskog tamjanovca primjenjuju se zbog djelovanja biološki aktivnih tvari u poboljšanju zdravstvenog stanja pacijenata i usporavanju progresije bolest. Osim toga, potrebno je osigurati visoku kvalitetu takvih proizvoda i njihovu sigurnu primjenu. Cilj ovog istraživanja bio je odrediti koncentraciju antimona, barija i bakra u dodacima prehrani korištenjem metode grafitne atomske apsorpcijske spektrometrije te utvrditi jesu li dobivene koncentracije unutar dopuštenih granica prema ICH Q3D smjernicama. Dobiveni rezultati upućuju na prisutnost barija i bakra u svim uzorcima, dok je koncentracija antimon u nekim uzorcima bila ispod granice određivanja. Osim toga, dnevni unos ispitivanih elementarnih onečišćenja bio je ispod PDE vrijednosti, što upućuje na kvalitetu dodataka prehrani bez potencijalnih negativnih posljedica ovih metala za pacijente koji ih koriste.The number of people suffering from inflammatory bowel diseases is constantly increasing. These patients often use different dietary supplements to support drug therapy itself. Dietary supplements containing plant species such as turmeric, green chiretta, and Indian frankincense are used due to the effect of biologically active substances in improving patients' health and slowing down disease progression. In addition, it is necessary to ensure the high quality of such products and their safe use. This research, which aimed to determine the concentration of antimony, barium, and copper in dietary supplements, provides reassuring findings. The results indicate the presence of barium and copper content in all samples, while the antimony concentration in some samples was below the detection limit. Furthermore, the daily intake of the examined elemental impurities was below the PDE value, confirming the safety and quality of these dietary supplements and alleviating any concerns about the potential negative consequences of these metals for the patients who use them
Determination of essential oil content and composition in coriander (Coriandrum sativum L.)
No full textKorijandar (Coriandrum sativum L.) je aromatična zeljasta biljka koja pripada porodici štitarki
(Apiaceae). Plodovi se koriste kao začin, a poznato je da posjeduju i ljekovita svojstva kao što su
antibakterijska, antifungalna, antidijabetička, hipolipemijska i hepatoprotektivna. U okviru ovog
diplomskog rada provedena je kvalitativna i kvantitativna fitokemijska analiza eteričnog ulja u osam
komercijalno dostupnih uzoraka korijandrovog ploda s hrvatskog tržišta. Farmakopejskom metodom
destilacije pomoću vodene pare utvrđeno je da analizirani uzorci plodova in toto sadrže 4,14 mL/kg
- 17,17 mL/kg eteričnog ulja, a uzorci plodova u in pulvere 9,12 mL/kg – 14,13 mL/kg eteričnog ulja.
Svi analizirani uzorci farmaceutske su kakvoće s obzirom na farmakopejski zahtjev za sadržajem
najmanje 3 mL/kg eteričnog ulja. Analiza izoliranog eteričnog ulja provedena metodom plinske
kromatografije spregnute s tandemskom spektrometrijom masa (GC-MS/MS) pokazala je da je
glavna sastavnica korijandrovog eteričnog ulja linalol (61,83 % - 87,73 %). Ostale značajnije
zastupljene sastavnice su γ-terpinen (3,29 % - 9,32 %), α-pinen (0,74 % - 7,15 %), kamfor (4,08 % -
6,12 %), geranil acetat (2,96 % - 6,29 %), p-cimen (0,74 % - 3,01 %), limonen (0,60 % - 4,10 %),
geraniol (0,15 % - 3,50 %) i α-terpineol (0,30 % - 0,50 %). Rad ukazuje na važnost osiguravanja
kakvoće biljnih droga koji se koriste u fitoterapiji i aromaterapiji, u cilju postizanja učinkovite i
sigurne primjene.Coriander (Coriandrum sativum L.) is an aromatic herbaceous plant belonging to the Apiaceae
family. The fruits are used as a spice and are known to possess medicinal properties such as
antibacterial, antifungal, antidiabetic, hypolipidemic, and hepatoprotective effects. This diploma
thesis conducted a qualitative and quantitative phytochemical analysis of the essential oil in eight
commercially available samples of coriander seeds from the Croatian market. Using the
pharmacopoeial method of steam distillation, it was determined that the analyzed samples of fruits
in toto contain 4.14 mL/kg to 17.17 mL/kg of essential oil, while the samples of fruits in pulvere
contain 9.12 mL/kg to 14.13 mL/kg of essential oil. All analyzed samples meet pharmaceutical
quality standards, as they contain at least 3 mL/kg of essential oil according to pharmacopoeial
requirements. The analysis of the isolated essential oil, performed using gas chromatography coupled
with tandem mass spectrometry (GC-MS/MS), showed that the main component of coriander
essential oil is linalool (61.83% - 87.73%). Other significantly represented components include γ-
terpinene (3.29% - 9.32%), α-pinene (0.74% - 7.15%), camphor (4.08% - 6.12%), geranyl acetate
(2.96% - 6.29%), p-cymene (0.74% - 3.01%), limonene (0.60% - 4.10%), geraniol (0.15% - 3.50%),
and α-terpineol (0.30% - 0.50%). This study emphasizes the importance of the quality of herbal drugs
used in phytotherapy and aromatherapy to ensure their effective and safe use
Determination of osmolality in isotonic drinks
No full textMnogi sportaši i tjelesno aktivni pojedinci koriste izotonične napitke kako bi osigurali pravilnu
hidrataciju tijekom intenzivnih fizičkih aktivnosti. Prema zahtjevu Europske agencije za sigurnost
hrane (eng. European Food Safety Authority, EFSA), izotonični napitci trebaju imati osmolalnost
u rasponu od 270 do 330 mOsm/kg, što odgovara osmolalnosti tjelesnih tekućina u ljudi. Na
hrvatskom su tržištu dostupni brojni sportski napitci koji se označavaju kao izotonični i
namijenjeni su tjelesno aktivnim pojedincima. U ovome je radu izmjerena osmolalnost izotoničnih
napitaka (n=18) dostupnih na hrvatskom tržištu. Dobivene su vrijednosti uspoređene s intervalom
izotoničnosti koji je propisala EFSA. Osmolalnost uzoraka izotoničnih napitaka mjerena je
krioskopskim osmometrom, metodom koja se temelji na određivanju točke ledišta. Trinaest
uzoraka izotoničnih napitaka imalo je vrijednost osmolalnosti u rasponu od 279 do 330 mOsm/kg,
što je bilo u skladu s propisanim kriterijima izotoničnosti. Pet uzoraka deklariranih kao izotonični
napitci imalo je osmolalnost u rasponu od 331 do 373 mOsm/kg, što je odgovaralo hipertoničnim
napitcima i, prema zahtjevima EFSA-e, ne bi se smjeli označavati kao izotonični. Prisutnost
napitaka s oznakom izotoničnosti koji ne udovoljavaju propisanim zahtjevima ukazuje na potrebu
za strožom kontrolom izotoničnih napitaka na hrvatskom tržištu.Many athletes and physically active individuals use isotonic drinks to maintain adequate hydration
during intense physical activities. According to the European Food Safety Authority (EFSA),
isotonic drinks should exhibit an osmolality between 270 and 330 mOsm/kg, corresponding to the
osmolality of human body fluids. Numerous sports drinks labeled as isotonic and intended for
physically active individuals are available on the Croatian market. In this study, the osmolality of
isotonic drinks (n=18) available on the Croatian market was measured. The obtained values were
compared with the isotonic range prescribed by EFSA. The osmolality of the isotonic drink
samples was determined using a cryoscopic osmometer, which measures osmolality based on the
freezing point depression method. Thirteen samples of isotonic drinks had osmolality values
ranging from 279 to 330 mOsm/kg, which complied with the prescribed isotonicity criteria.
However, five samples labeled as isotonic exhibited osmolality values ranging from 331 to 373
mOsm/kg, which corresponded to hypertonic drinks and, according to EFSA requirements, should
not be labeled as isotonic. The presence of drinks labeled as isotonic that don't meet the prescribed
requirements indicates the need for more rigorous control of isotonic drinks on the Croatian
market
Synthesis and characterization of new derivatives of tetrahydropyrrolo[3,4-b]indole with propargyl and tert-butyl ester groups as precursors of hybrid molecules with potential antimalarial activity
No full textMalarija je infektivna bolest tropskih i subtropskih krajeva koja svake godine bilježi porast mortaliteta, a nemogućnost
kontrole širenja bolesti predstavlja veliki izazov. Ovaj rad obuhvaća sintezu i karakterizaciju novih derivata
tetrahidropirolo[3,4-b]indola s propargilnom i tert-butilnom esterskom skupinom, kao prekursora hibridnih molekula s
potencijalnim antimalarijskim djelovanjem. Izabrani izocijanidni derivati dobiveni su iz odgovarajućih aminokiselina.
Propargilni esteri DL-alanina i L-fenilalanina (8, 13) pripravljeni su u 3 koraka, dok je tert-butilni ester DL-alanina (3)
pripravljen u jednom sintetskom koraku. Potom je amino-skupina pripravljenih estera (3, 8, 13) prevedena u
formamidnu, a u posljednjem koraku formamidi su prevedeni u odgovarajuće izocijanidne derivate (5, 10, 15). Dobiveni
spojevi (16, 17, 18) korišteni su u reakciji dearomatizacije N-tosil-3-nitroindola (2) koji je prethodno pripravljen iz
indola u 2 koraka. Zbog nestabilnosti spojeva dobivenih dearomatizacijom provedena je in situ redukcija uz NaBH3CN.
U daljnjim istraživanjima, koja prelaze okvire ovog rada, click-reakcijom propargilne skupine pripravljenog spoja i
molekule koja sadrži funkcionalnu skupinu azid sintetizirat će se novi hibridni spojevi potencijalnog anitmalarijskog
djelovanja.Malaria is an infectious disease found in tropical and subtropical regions, which records an annual increase in mortality,
and the inability to control the spread of the disease presents a major challenge. This paper covers the synthesis and
characterization of new derivatives of tetrahydropyrrolo[3,4-b]indole with propargyl and tert-butyl ester groups as
precursors of hybrid molecules with potential antimalarial activity. The selected isocyanide derivatives were obtained
from the corresponding amino acids. Propargyl esters of DL-alanine and L-phenylalanine (8, 13) were prepared in three
steps, while the tert-butyl ester of DL-alanine (3) was synthesized in a single synthetic step. The amino group of the
prepared esters (3, 8, 13) was then converted to a formamide group, and in the final step, the formamides were converted
into the corresponding isocyanide derivatives (5, 10, 15). The obtained compounds (16, 17, 18) were used in the
dearomatization reaction of N-tosyl-3-nitroindole (2), which was previously synthesized from indole in two steps. Due
to the instability of the compounds obtained through dearomatization, in situ reduction was performed using NaBH3CN.
In further research, beyond the scope of this work, new hybrid compounds with potential antimalarial activity will be
synthesized by performing a click reaction between the propargyl group of the prepared compound and a molecule
containing an azide functional group
The effect of botulinum toxin type a on neural activation in the region of the trigeminal caudal nucleus in a model of inflammatory pain induced by formalin
No full textBol kroničnog trajanja je veliki problem u svijetu i u mnogim se slučajevima ona ne može uspješno kontrolirati konvencionalnim analgeticima. Tijekom posljednja tri desetljeća u nekliničkim i kliničkim istraživanjima pokazan je potencijal botulinum toksina tipa A (BT-A) u nanogramskim dozama u smanjenju i dugotrajnoj kontroli kronične boli različite etiologije. Međutim, njegov mehanizam djelovanja na patološku bolnu preosjetljivost nije do kraja poznat. Dosadašnja istraživanja pokazala su da BT-A s perifernog mjesta primjene retroaksonalnim transportom putuje u središnji živčani sustav gdje modulira djelovanje različitih neurotransmiterskih sustava, da bi najnovija istraživanja sugerirala i njegov među-sinaptički prijenos. U ovom diplomskom radu je istraženo središnje antinociceptivno djelovanje periferno jednostrano primjenjenog BT-A u modelu upalne boli izazvane bilatralnom primjenom formalina u području njuške štakora. Praćenjem ekspresije c-Fos-a pokazano da BT-A smanjuje neuralnu aktivaciju u neuronima TNC-a na strani na kojoj je primjenjen, ali i na suprotnoj strani, pri čemu neutralizirajući antitoksin za BT-A poništava to djelovanje na obje strane. Rezultati ovog rada se slažu s do sada provedenim istraživanjima i upućuju na među-sinaptički prijenos kao važan čimbenik u kompleksnom mehanizmu antinociceptivnog djelovanja BT-A.Chronic pain is big health-care issue worldwide, and in many cases, it cannot be completely resolved with conventional analgetics. Over the past three decades, non-clinical and clinical research demonstrated that in nanogram concentrations, botulinum toxin type A (BT-A) has potential to alleviate and long-term control chronic pain of various etiologies. However, its mechanism of action on pathological pain hypersensitivity is not fully understood. So far, researchers have shown that BT-A travels from peripheral application site to central nervous system via retrograde axonal transport, where it modulates different neurotransmitter systems, and the latest research suggests transynaptic transmission. In this master’s thesis, the central antinocieptive action of unilaterally, peripherally applied BT-A, was investigated in the inflammatory pain model caused by bilateral application of formalin to the rat whisker pad. By monitoring expression of c-Fos as a marker of neural activation, it was shown that BT-A reduces neural activation in the neurons of the TNC region on the side of the application as well as on the opposite side, whilst neutralizing BT-A antitoxin reverses BT-A effect on both sides. Obtained results in this master’s thesis are consistent with previous studies and indicate that transynaptic transmission is one of the important factors in the complex antinociceptive mechanism of BT-A
Cost analysis of autoimmune disease pemphigus vulgaris
No full textVulgarni pemfigus (VP) je rijetka autoimuna bolest iz skupine buloznih dermatoza. Autoimune bulozne dermatoze
bolesti su epidermalnog i subepidermalnog područja koje karakterizira stvaranje protutijela na strukturne proteine i
adhezivne molekule uslijed čega nastaju mjehuri na koži i/ili sluznicama. Kod VP-a patofiziološke promjene događaju
se u epidermisu, dok je kod buloznog pemfigoida (BP) zahvaćeno subepidermalno područje.
Liječenje VP-a zasniva se na terapiji sistemskim kortikosteroidima koja se većinom primjenjuje oralno, iako je moguća
i intravenska primjena. Kod liječenja BP-a terapija kortikosteroidima je uglavnom topikalna s primjenom lijeka na
području cijele kože. U obje bolesti moguća je primjena adjuvantne terapije imnuosupresivima kao što su azatioprin i
mikofenolat, te biološke terapije, primarno monoklonskog protutijela rituksimaba.
VP rijetka je bolest od koje godišnje u Republici Hrvatskoj obolijeva 9 osoba po milijun stanovnika, no zbog velikog
udjela hospitalizacija te korištenja pojedinih skupih lijekova ova bolest proizvodi nemali trošak za HZZO. Ukupni
izravni trošak VP-a procijenjen je ovom analizom tako da su zbrojeni troškovi hospitalizacije koji se plaćaju prema
DTS-u, troškovi DTP-a u PZZ i SZZ koji nisu uključeni u trošak hospitalizacije, te trošak lijekova koji se primjenjuju
nevezano za hospitalizaciju. Također je zasebno procijenjen trošak svakog lijeka koji se primjenjivao prilikom
hospitalizacije radi detaljnijeg prikaza troškova u zdravstvu. Kao najskuplji lijek primjenjivan tijekom hospitalizacije
pokazalo se monoklonsko protutijelo rituksimab za koji je po pacijentu tijekom hospitalizacije utrošeno prosječno
1.766,17 EUR. Ukupni trošak hospitalizacija temeljen je na DTS šifri J68A te je množenjem cijene te šifre s brojem
pacijenata u RH dobiven ukupni trošak hospitalizacije od 93.529,63 EUR. Trošak DTP-a dobiven je zbrajanjem
pojedinih postupaka koji su korišteni u PZZ i SZZ čime je procijenjen ukupni iznos od 185.682,35 EUR. Prilikom
izračuna troška lijekova u izvanbolničkoj terapiji ponovno se isticao rituksimab čiji je trošak od 440.005,39 EUR
nadilazio ukupan zbroj ostalih troškova u liječenju VP-a. U konačnici je procijenjen ukupan trošak liječenja VP-a koji
je iznosio 770.495,22 EUR godišnje.Pemphigus vulgaris (PV) is a rare autoimmune disease from the group of bullous dermatoses. Autoimmune bullous
dermatoses are of the epidermal and subepidermal area, characterized by the formation of antibodies against structural
proteins and adhesive molecules, resulting in the formation of blisters on the skin and/or mucous membranes. In pemphigus
vulgaris, pathophysiological changes occur in the epidermis, whereas in bullous pemphigoid (BP) the subepidermal area
is affected.
The treatment of PV is based on systemic corticosteroid therapy, which is mostly administered orally, although intravenous
administration is also possible. In the treatment of BP, corticosteroid therapy is mainly topical with the application of the
drug over the entire skin area. In both diseases, it is possible to use adjuvant therapy with immunosuppressants such as
azathioprine and mycophenolate, as well as biological therapy, primarily the monoclonal antibody rituximab.
PV is a rare disease that affects 9 people per million inhabitants annually in the Republic of Croatia, but due to the high
proportion of hospitalizations and the use of certain expensive drugs, it leaves a potentially large mark on HZZO. The
total direct cost of PV was estimated in this analysis in by adding up the costs of hospitalization paid according to DTS,
the costs of DTP in PHC and SHC that are not included in the cost of hospitalization, and the cost of drugs that are applied
unrelated to hospitalization. Also, the cost of each drug that was used during hospitalization was separately estimated for
a more detailed presentation of healthcare costs. The monoclonal antibody rituximab proved to be the most expensive drug
used during hospitalization, for which an average of 1,766.17 EUR was spent per patient. The total cost of hospitalization
is based on the DTS code J68A, and by multiplying the price of that code with the number of patients in the Republic of
Croatia, the total cost of hospitalization is 93,529.63 EUR. The cost of DTP was obtained by adding up the individual
procedures that were used in PHC and SHC, which estimated the total amount of 185,682.35 EUR. When calculating the
cost of drugs in outpatient therapy, rituximab stood out again, whose cost of 440,005.39 EUR exceeded the total sum of
other costs in the treatment of PV. In the end, the total estimated cost for PV treatment amounted to 770.495,22 EUR per
year
Beta-carboline ring structure optimisation: the way towards new hybrid compounds with potential antimalary activity
No full textMalarija je zarazna bolest koju uzrokuju različite vrste parazita roda Plasmodium, a od koje umire sve veći broj ljudi.
Harmala alkaloidi β-karbolinskog tipa identificirani su kao spojevi uzori za razvoj novih klasa antimalarika. Promjena
strukture postojećih antimalarika uvođenjem β-karbolinskog motiva pokazala se učinkovitom strategijom za pojačanje
antimalarijske aktivnosti, kao i potencijalno smanjenje rezistencije. S obzirom na poboljšanu antimalarijsku aktivnost
prethodno sintetiziranih hibrida β-karbolina i poznatih antimalarika, u okviru ovog rada odlučili smo modificirati β-
karbolinski prsten. U svrhu njegove priprave, bilo je potrebno sintetizirati N-tosil nitroindol te seriju aminokiselina
modificiranih izocijanidnom skupinom. Dearomatizacijom N-tosil nitroindola serijom aminokiselina modificiranih
izocijanidnom skupinom dobiven je novi triciklički prsten (heksahidropirolo[3,4-b]indol). Novosintetizirani, različito
supstituirani, triciklički prsteni su in situ alkilirani N-propargil indolom ili indolom čime su dobivene ciljne molekule
(16-18). Strukture svih novosintetiziranih molekula potvrđene su standardnim spektroskopskim metodama (1H i 13C
NMR). Dobivene molekule će se u nastavku istraživanja koristiti kao fragmenti za tvorbu hibridnih spojeva s poznatim
antimalaricima metodom Cu(I) katalizirane alkin-azid cikloadicije (klik-reakcijom).Malaria is an infectious disease caused by various species of parasites of the Plasmodium genus, and from which an
increasing number of people are dying. Harmala alkaloids of the β-carboline type have been identified as lead
compounds for the development of new classes of antimalarials. Changing the structure of existing antimalarials by
introducing a β-carboline motif has proven to be an effective strategy for enhancing antimalarial activity, as well as
potentially reducing resistance. Given the improved antimalarial activity of previously synthesized β-carboline hybrids
and common antimalarials, we decided to modify the β-carboline ring in this work. For its preparation, it was necessary
to synthesize a N-tosyl nitroindole and a series of amino acids modified with an isocyano group. A new tricyclic ring
(hexahydropyrrolo[3,4-b indole]) was obtained by dearomatization of N-tosyl nitroindol with a series of amino acids
modified with an isocyano group. Newly synthesized, differently substituted, tricyclic rings were in situ alkylated with
N-propargyl indole or indole to obtain the target molecules (16-18). The structures of all newly synthesized molecules
were confirmed by standard spectroscopic methods (1H and 13C NMR). The obtained molecules will be used in the
continuation of the research as fragments for the formation of hybrid compounds with known antimalarials by the
method of Cu(I) catalyzed alkyne-azide cycloaddition (click-reaction)
Macroelements in formulated dietary supplements for the treatment of inflammatory bowel diseases
No full textDodaci prehrani sadrže brojne minerale koji su vrlo važni za očuvanje fizioloških funkcija ljudskog organizma, a samim time i za očuvanje zdravlja. Kod bolesnika s upalnim bolestima crijeva dodatan unos minerala ublažava simptome uzrokovane deficitom minerala. Zbog toga je cilj ovog rada bio odrediti sadržaj makroelemenata (Na, K, Ca, Mg) u tržišno dostupnim dodacima prehrani za liječenje upalnih bolesti crijeva. Ispitivanje je provedeno plamenom tehnikom - atomskom apsorpcijskom spektrometrijom nakon postupka vlažnog spaljivanja mikrovalnom digestijom. Dobiveni rezultati su pokazali da je sadržaj analiziranih makroelemenata izrazito varijabilan. Kalij je bio najzastupljeniji mineral u ispitivanim uzorcima i imao je puno veću varijabilnost od kalcija, natrija i magnezija. Tvrde kapsule su sadržavale više koncentracije makroelemenata nego meke kapsule. I na kraju je važno za naglasiti kako se analiziranim dodacima prehrani primjenim u preporučenim i maksimalnim dozama unose manje količine od preporučenih za pojedini element, te tako nema opasnosti od njihove potencijalne toksičnosti.Dietary supplements contain numerous minerals that are very important for preserving the physiological functions of the human body and, thus for preserving health. In patients with inflammatory bowel diseases, additional intake of minerals alleviates symptoms caused by mineral deficiency. Therefore, this work aimed to determine the content of macroelements (Na, K, Ca, Mg) in commercially available dietary supplements for the treatment of inflammatory bowel diseases. The test was carried out using the flame technique - atomic absorption spectrometry after the process of wet burning with microwave digestion. The obtained results showed that the content of analyzed macroelements is highly variable. Potassium was the most abundant mineral in the tested samples and they have a much higher variability than calcium, sodium and magnesium. Hard capsules contain more concentration of macronutrients than soft capsules. Finally, it is important to emphasize that when used in recommended and maximum doses, the analyzed dietary supplements are taken in smaller amounts than recommended for each element, so there is no danger of their potential toxicity
Determination of osmolality in non-alcoholic beer
No full textPrema Europskoj agenciji za sigurnost hrane (eng. European Food Safety Authority, EFSA) osmolalnost izotoničnih pića namijenjenih sportašima i tjelesno aktivnim pojedincima trebala bi iznositi od 270 do 330 mOsm/kg vode. U ovome je radu izmjerena osmolalnost bezalkoholnog piva (n = 14) i Radler piva s niskim sadržajem alkohola (n = 8) dostupnih na hrvatskom tržištu te su dobivene vrijednosti uspoređene s intervalom izotoničnosti koji je odredila EFSA. Osmolalnost devet uzoraka bezalkoholnog piva u rasponu od 279 do 324 mOsm/kg vode zadovoljavala je kriterij izotoničnosti prema EFSA-i. Uzorci Radler piva imali su vrijednosti osmolalnosti u rasponu od 353 do 914 mOsm/kg vode što je odgovaralo vrijednostima hipertoničnih otopina. U pojedinim se europskim državama neka bezalkoholna piva deklariraju i/ili oglašavaju kao izotonična te se stoga preporučuju sportašima i tjelesno aktivnim pojedincima, dok bezalkoholna piva dostupna na hrvatskom tržištu uglavnom ne sadrže deklaraciju o izotoničnosti. Rezultati ankete provedene među studentima Kineziološkog fakulteta Sveučilišta u Zagrebu (n = 52) pokazali su potrebu za deklariranjem izotoničnosti bezalkoholnog piva. S obzirom na utvrđenu izotoničnost većine ispitanih uzoraka bezalkoholnog piva te njegovu potencijalnu primjenu tijekom sportskih aktivnosti, potrebno je uskladiti propise o deklariranju izotoničnosti bezalkoholnog piva na hrvatskom tržištu.According to the European Food Safety Authority (EFSA), the osmolality of isotonic beverages intended for athletes and physically active individuals should range from 270 to 330 mOsm/kg of water. In this study the osmolality of non-alcoholic beers (n = 14) and low-alcohol Radler beers (n = 8) available on the Croatian market was measured and compared to the isotonicity range defined by EFSA. The osmolality of nine non-alcoholic beer samples ranged between 279 and 324 mOsm/kg of water and thus met the isotonicity requirement suggested by EFSA. The Radler beer samples had osmolality values ranging from 353 to 914 mOsm/kg of water, which corresponded to the values of hypertonic solutions. In some European countries, certain non-alcoholic beers are labeled and/or advertised as isotonic and are therefore recommended to athletes and physically active individuals. However, non-alcoholic beers available on the Croatian market are generally not labeled as isotonic. The results of a survey conducted among students of the Faculty of Kinesiology at the University of Zagreb (n = 52) showed a need for labeling the isotonicity of non-alcoholic beer. Given that the majority of non-alcoholic beer samples tested meet the EFSA-defined criteria for isotonicity and their potential use during sports activities, it is necessary to harmonize regulations concerning isotonicity labeling of non-alcoholic beer on the Croatian market