Search

Uz minimalni utrošak materijalnih sredstava, bez zagađivanja životne sredine i ugrožavanja ljudi, dobit će se dragocjeni podatci koji će biti dostupni širokoj istraživačkoj zajednici, posebno kroz objavljene publikacije. Rezultati projekta omogućit će dobivanje baze za in vitro ispitivanja odabranih spojeva na SARS- CoV-2 koja će se upotrebljavati u svrhu budućih in vitro ispitivanja. Rezultati će se također upotrebljavati za istraživanja i edukaciju studenata u okviru završnih radova

Xanthene derivatives represent cyclic, organic compounds that can be natural, semi-synthetic and synthetic origin. These compounds become very interesting because of various pharmacological activities such as antibacterial, antiviral and anti-inflammatory properties. Furthermore, they have been utilized as antagonists for drug-resistant leukemia lines and in photodynamic therapy. They are also applied as dyes in laser technology and pH sensitive fluorescent materials for visualization of biomolecules. Because of new diseases in veterinary medicine, application of these compounds can be very useful and literature describes activity of similar compunds in veterinary research field. In this review the most important activity of xanthen derivatives such as antibacterial, antifungal, antihelmintic, antiprotozoal, anticancerogenic and antidiabetic activity and mechanism of their action are presented., Ksanten türevleri, doğal, yarı sentetik ve sentetik kökenli olabilen siklik, organik bileşikleri temsil eder. Bu bileşikler, antibakteriyel, antiviral ve antienflamatuar özellikler gibi çeşitli farmakolojik aktiviteler nedeniyle dikkat çekmektedirler. Ayrıca, ilaca dirençli lösemi hatları için ve fotodinamik tedavide antagonistler olarak kullanılmaktadırlar. Ayrıca lazer teknolojisinde boyalar ve biyomoleküllerin görselleştirilmesi için pH'a duyarlı floresan malzemeler olarak uygulanırlar. Veteriner hekimlik alanında yeni hastalıklar nedeniyle, bu bileşiklerin uygulanması çok faydalı olabilir ve literatürde Veteriner araştırma alanındaki benzer bileşiklerin aktivitesi açıklanmaktadır. Bu derlemede ksanten türevlerinin antibakteriyel, antifungal, antihelmintik, antiprotozoal, antikanserojenik ve antidiyabetik aktivite gibi en önemli aktiviteleri ve etki mekanizmaları sunulmuştur.

Nucleoside analogues represent an important class of compounds of wide application range in antiviral and antitumor therapy. A regular procedure in early phases of new drugs development includes assessment of cytotoxicity and genotoxicity (mutagenicity). Here we report the synthesis of two novel C-5 hydroxypropyl pyrimidine nucleosides bearing side chains like those present in drugs already used in therapy (penciclovir and cidofovir). To confirm structures of the newly synthesized compounds FT-IR, HPLC-MS and NMR spectroscopy in solution were used. New hydroxypropyl pyrimidine nucleosides were N-3-(2, 3-dihydroxypropyl)-5- (3-hydroxypropyl)pyrimidine-2, 4-dione and N-3- (4-hydroxy-3-(hydroxymethyl)butyl)-5-(3- hydroxypropyl)pyrimidine-2, 4-dione.Along with two new, we have also tested three previously synthesized nucleosides for genotoxicity and cytotoxicity using cytokinesis-block micronucleus (CBMN) assay on human peripheral blood lymphocytes. Not many studies so far used the same cell model and CBMN assay to determine cyto-/genotoxicity of pyrimidine nucleosides. Results of CBMN assay did not indicate statistically significant cyto-/genotoxicity towards human peripheral blood lymphocytes. Since preliminary testing did not suggest significant genotoxic or cytotoxic potency of novel hydroxypropyl pyrimidine nucleosides, they are excellent candidates for further biological evaluation, primarily as antiviral agents.

Tirozinaza je metaloenzim koji katalizira hidroksilaciju monofenola u katehole i oksidaciju katehola u o-kinone. Ključni je enzim melanogeneze u životinja i ljudi te su inhibitori humane tirozinaze potencijalni lijekovi u poremećajima hiperpigmentacije. Sigurni i učinkoviti inhibitori tirozinaze su od velikog značaja kao potencijalna nova skupina lijekova. Cilj ovog istraživanja je ispitivanje inhibitornog djelovanja novosintetiziranih spojeva derivata 2, 2’-fenilmetilen-bis(5, 5- dimetilcikloheksan-1, 3-diona) na tirozinazu. Ispitivano je 5 derivata (1e, 2e, 4e, 5e i 6e). Aktivnost tirozinaze i inhibitorni učinci derivata 2, 2’- fenilmetilen-bis(5, 5-dimetilcikloheksan-1, 3-diona) ispitivali su se UV-Vis spektrofotometrijom, na sobnoj temperaturi. Mjerila se apsorbancija produkta dopakroma na 475 nm. Ispitivana otopina se sastojala od L-DOPA-e (supstrat enzima), derivata čiju inhibitornu aktivnost ispitujemo i tirozinaze. Kao pozitivna kontrola korištena je kojična kiselina, kao već poznati inhibitor tirozinaze. Ostatna aktivnost tirozinaze je prikazana kao apsorbancija produkta nakon 15 minuta inkubacije s ispitivanim spojevima tj. započinjanja reakcije. Dva derivata 2, 2’-fenilmetilen-bis(5, 5-dimetilcikloheksan-1, 3-diona) su pokazala statistički značajnu inhibiciju tirozinaze nekompetitivnog tipa (4e i 2e). Maksimalan postotak inhibicije nakon 15 minuta iznosio je 13% (spoj 2e). Pri istim uvjetima kojična kiselina je inhibirala 70% enzimske aktivnosti. Potrebna su dodatna istraživanja kako bi se utvrdila toksičnost ispitanih derivata te njihova vrijednost kao inhibitora tirozinaze

Thymoquinone (TQ) is a natural benzoquinone with various biological and medicinal activities. The main disadvantage of TQ is its low aqueous solubility. In the present work we report the synthesis and biological activities of TQ derivative, 3-aminothymoquinone (ATQ). ATQ was prepared according to published literature reports, with slight modifications. The structure was identified by elemental analysis and characterized in solution by mass spectrometry and NMR spectroscopy. Antimicrobial activity was determined against four Gram-positive and four Gram-negative bacteria strains and three fungi using diffusion and micro-dilution methods. It was observed that antibacterial activity is diminished in case of ATQ when compared to TQ. On the other hand, ATQ showed strong antifungal activity in all tested fungi (Candida albicans ATCC 10231, Saccharomyces cerevisiae ATCC 9763 and Aspergillus brasiliensis ATCC 16404) with minimal inhibitory concentration (MIC) values significantly lower when compared to TQ and Nystatin which was used as the reference drug. Antiproliferative activity of TQ and ATQ was evaluated in five different cell lines: SW620 (metastatic human colon adenocarcinoma), CFPAC (ductal pancreatic adenocarcinoma), HepG2 (hepatocellular carcinoma), HeLa (cervical adenocarcinoma) and WI38 (human lung fibroblasts). ATQ had stronger effects in all tested cell lines when compared to TQ. In conclusion, ATQ, which is the C-3 amino derivative of TQ, exerts significantly higher antifungal and antitumor activity, when compared to parent compound.

Xanthene derivatives are important compounds because of their proven biological activities. Seven 14-aryl-14H-dibenzoxanthenederivatives were synthesized by reliable solvent-free synthesis procedure using iron (III) chloride hexahydrate as a catalyst. Three synthesized derivatives possess antibacterial activities against different bacteria. Compound 14-(2’, 5’- dimethoxyphenyl)-14H-dibenzo[a, j]xanthene(3) showed best activity against Escherichia coliand Staphylococcus aureus with MIC 0.616 mg/mL. Docking study for the most potent compound was carried out by taking amino terminal domain of enzyme I as a target for antibacterial activity against Escherichia coli and it was shown that binding energy of 3 was similar to amikacin’s (around –4.2 kcal/mol) used as a referent drug, although bound on a different sites on enzyme.

According to principles of solvent-free chemistry, it would be ideal to attain best yields of product using the least expensive and non toxic catalyst. Syntheses of 14-aryl substituted dibenzoxanthene derivatives in solvent-free conditions have been already reported in literature, using various catalysts. Iron (III) chloride hexahydrate (FeCl3×6H2O) is one of efficient and non toxic catalyst which can be used in this type of syntheses. Solvent-free chemistry principles are used for synthesis of substituted dibenzoxanthenes with alkyl chain on aryl part of molecule. Dibenzoxanthene derivative with trifluoromethyl group as substituent posses good antimicrobial activity. So, in the future, will be synthesized more structural analogues of dibenzoxanthene, to determine which substituents substantially increases their antibacterial activity.

Udžbenik za studente farmacije - kolegij Farmaceutsak kemija 1.

Quantum mechanics provides the mathematical apparatus for determining numerous properties of chemical systems, whereas computer programs carry out the necessary calculations. Guaiazulene is starting compound in many reactions for obtaining azulene derivatives with significant pharmacological activity. Calculations for guaiazulene were done using software Spartan 10. The guaiazulene molecule was optimized by B3LYP/6-31G* method. Chemical hardness, total energy, electronic chemical potential and electrophilicity were calculated and used to predict relative stability and reactivity of guaiazulene. Results of DFT study showed that guaiazulene possess good reactivity and behaves as nucleophile. These results were in good accordance with former experimental research about this compound.

Reakcijom nukleofilne adicije sintetiziranog prekursora, 3-acetil-4-hidroksi-2H-1- benzopiran-2-ona, s različitim aromatskim aldehidima, u prisustvu baznih katalizatora piridina i piperidina, sintetizirani su novi derivati 4-hidroksikumarina, 4-hidroksi-3-(3- (4- etoksifenil)prop-2-enoil)-2H-1-benzopiran- 2-on i 4-hidroksi-3-(3-(4- trifluormetilfenil)prop-2- enoil)-2H-1- benzopiran-2-on. Preliminarna mikrobiološka ispitivanja su pokazala da oba spoja imaju izrazito baktericidno djelovanje. Strukture spojeva, C20H16O5 i C19H11O4F3, su određene različitim 1D i 2D tehnikama NMR. Ovisnost 1H NMR kemijskih pomaka hidroksilne skupine o temperaturi i koncentraciji ukazuje na postojanje jake intramolekulske vodikove veze O −H•••O u molekulama istraženih spojeva.

The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. ISSN:1420-3049

Series of synthesized xanthen-3-one derivatives were analyzed for thermal characteristics by differential scanning calorimetry (DSC), as well as for crystallinity using X-ray powder diffraction. Xanthen-3-one derivatives are prepared according to the well known procedure which includes two-fold Friedel-Crafts alkylation. The aim of this research was to determine purity and crystallinity of synthesized xanthen-3-one derivatives. Thermograms of synthesized compounds showed that compounds have purity above 98%, while crystallographic analysis of powder showed that the compounds have a 10-30% crystalline form.

Sintetiziranim 4-hidroksikumarinima ispitana je antimikrobna aktivnost na 5 mikroorganizama, kao i na gljivicu Candida Albicans.

AIDS (Acquired Immunodeficiency Syndrome) is a long-term infection which starts with entry of human immunodeficiency virus (HIV) in blood circulation, and during untreated infection comes to gradual and irretrievable reducing of immunological system, which leads to the death, caused by different kinds of additional infections and malignant tumours. It is shown that appropriate therapy could prevent multiplication of HIV viruses, appearance of disease and considerable reduced mortality. In clinical experiments combined therapy have shown good efficiency on clinical or laboratory parameters. Knowing characteristics, mechanisms of action of anti-HIV medicines make a therapy of AIDS easier.

In this work, several quantitative QSPR/QSAR models for predicting the properties and activity of new synthesized coumarins are described and evaluated.

In this work, several quantitative QSPR/QSAR models for predicting the properties and activity of new synthesized 4-hydroxycoumarins are described and evaluated.

Sinteza derivata kumarina danas je od posebnog značaja, jer je dokazano da djeluju i na HIV virus. Dobiveni rezultati korišteni su za istraživanje odnosa između strukture i svojstava, odnosno aktivnosti istraživanih spojeva. U tu svrhu, pomoću vlastitog programskog paketa MOLSTRU, izračunati su topologijski indeksi.