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1

Glass and glass-ceramic porous materials for biomedical applications

Kędzia Olga, Lubas Małgorzata, Dudek Agata

System Safety : Human - Technical Facility - Environment

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2023

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Vol. 5, iss. 1

302--310

EN

Biosilicate glasses and glass-ceramic materials obtained on their basis are an important research area in tissue engineering due to their ability to regenerate bones. The most important features of bioactive glasses include: the ability to biodegrade and high bioactivity. Appropriate porosity, pore size, surface structure and topography, chemical composition and ion release kinetics, as well as mechanical properties enable the adhesion of mesenchymal cells and their differentiation towards osteoblast cells and stimulate further proliferation and angiogenesis. This study concerns the subject of bioglass, in particular Bioglass 45S5 and glass-crystalline porous materials in the context of their properties enabling the reconstruction of bone tissue and possible applications. The article addresses crucial issues of shaping the properties of glass and glass crystalline porous structures by introducing changes in their composition and the method of their production, and also discusses the importance of foaming agents.

2

Nitrosubstituted analogs of isoxazolines and isoxazolidines: a surprising estimation of their biological activity via molecular docking

Zawadzińska Karolina, Gostyński Bartłomiej

Scientiae Radices

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2023

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Vol. 2, Iss. 1

25--46

EN

The biological activities in the field of antimicrobial application of trihalomethylated isoxazolines and isoxazolidines were investigated by means of molecular docking. In our work, we compared these two groups of heterocyclic compounds due to their strength of non-covalent binding affinity with several exemplary proteins that are known to partake in various biological processes. The obtained results show that the investigated compounds possess higher binding affinities to selected proteins than many hitherto known and applied compounds.

3

Synteza kilku nowych związków heterocyklicznych z chalkonów

Saeed Banan Borhan, Saeed Zainab Faiyq, Dawood Nagham M. Zaki

Przemysł Chemiczny

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2023

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T. 102, nr 9

884--894

PL

Przeprowadzono syntezę 1-(4-nitrofenylo)-3-fenyloprop-2-en-1-onu (chalkon) oraz dokonano jego konwersji z mocznikiem/tiomocznikiem w środowisku stężonego kwasu solnego do odpowiednio 4-(4-nitrofenylo)-6-fenylopirymidyno-2(1H)-onu (3) i do 4-(4-nitrofenylo)-6-fenylopirymidyno-2(1H)-tionu (4), lub w środowisku alkalicznym (etanolowym) do 4-(4-nitrofenylo)-6H-1,3-oksazyno-2-aminy (1) i 4-(4-nitrofenylo)-6-fenylo-6H-1,3-tiazyno-2-aminy (2). Aminy te przeprowadzono w związki diazoniowe i poddano reakcji z kilkoma drugorzędowymi aminami w celu otrzymania 2-(3,3-dialkilotriaz-1-en-1-ylo)-4-(4-nitrofenylo)-6-fenylo-6H-1,3-oksazyn/tiazyn (5-14). Ich strukturę potwierdzono metodami spektroskopowymi (IR, ¹H-NMR). Zbadano też aktywność biologiczną związków 1-7 w stosunku do bakterii Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli i Klebsiella spp. oraz drożdży Candida albicans. Dokonano również oceny ich farmakokinetyki i użyteczności dla chemii medycznej, a także wpływu na pracę serca. Stwierdzono, że związki 1, 2 i 4 wykazały dobrą aktywność biologiczną.

EN

1-(4-Nitrophenyl)-3-phenylprop-2-en-1-one (chalcone) was synthesized by condensation of benzaldehyde with 4-nitroacetophenone in alk. EtOH and then converted with urea or thiourea in concd. HCl soln. to 4-(4-nitrophenyl)-6-phenylpyrimidin-2(1H)-one or to 4-(4-nitrophenyl)-6-phenylpyrimidin-2(1H)-thione and in alk. EtOH to 4-(4-nitrophenyl)-6-phenyl-6H-1,3-oxazin/thiazin-2-amines. The amines were converted to resp. diazonium salts and reacted with sec. amines to obtain 2-(3,3-dialkyltriaz-1-en-1-yl)-4-(4-nitrophenyl)-6-phenyl-6H-1,3-oxazine\thiazine), where alkyldiazenyl substituents were: 2-ethylpiperidin-1-yldiazenyl, 9H-carbazol-9-yldiazenyl, morpholinodiazenyl, 3,3-diisobutyltriaz-1-en-1-yl and 3,3-dibutyltriaz-1-en-1-yl. The oxazines and thiazines were identified by IR and ¹H-NMR spectroscopies and studied for their biol. activity against Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli and Klebsiella spp. bacteria and Candida albicans yeast. The med. friendliness and pharmacokinetics of the molecules as well as their effects on heart functions were evaluated. The 4-(4-nitrophenyl)-6-phenylpyrimidin-2(1H)-thione and 4-(4-nitrophenyl)-6-phenyl-6H-1,3-oxazin/thiazin-2-amines showed good biol. activity.

4

Nukleozydo i oligonukleozydo boranofosfoniany : metody syntezy i wybrane właściwości biologiczne

Gołębiewska Justyna

Wiadomości Chemiczne

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2020

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[Z] 74, 7-8

477--506

EN

Interest in boron-containing compounds has grown in recent years due to their potential medicinal and biochemical applications. Nucleoside boranephosphonates are analogues of naturally occurring nucleoside phosphates in which one of the non- bridging oxygen atom has been replaced by a BH3 group [1]. This modification imparts unique biological properties to nucleotides and nucleic acids. DNA and RNA fragments containing boranephosphonate internucleotide linkages are resistant to various nucleases, stimulate the RNase H activity, and reveal high lipophilicity, which significantly enhances their cellular uptake [2]. The hydrolytic stability and nuclease resistance make these compounds attractive candidates in designing new therapeutics and medicinal diagnostics. Considering these characteristics nucleoside boranephosphonates constitute a promising class of nucleotide analogues worth exploring for biological purposes.

5

Fluorowany motyw w aktywnych biologicznie peptydomimetykach

Koroniak-Szejn Katarzyna, Rapp Magdalena

Wiadomości Chemiczne

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2020

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[Z] 74, 3-4

145--179

EN

Incorporation of fluorine atom or fluoroalkyl group into molecules, often induces a remarkable effect upon the physical and chemical properties leading to significant changes of its reactivity [1-5], therefore this modification is often used in the synthesis of drugs and biologically active compounds [6, 7]. The change in reactivity has far-reaching consequences, affects bond energy in the molecule, acidity and alkalinity, hydrogen bond formation and the geometry of the molecule [1-5]. The change in acid-base properties and polarity forced by a fluorine or fluorinated motif in the modified amino acid or peptide molecule has already found numerous applications in bioisosteric mimetics [9]. In addition, using a fluorine atom as a probe, conformation determination and stereochemistry of receptor interaction become more effective due to the possibility of using 19F NMR spectroscopy. The stereoselective introduction of fluorine atoms can therefore be exploited as a conformational tool for the synthesis of shape-controlled functional molecules. Particular attention has been paid to fluorinated peptidomimetics due to the huge variety of their biological activity. Proteins play a significant role in drug design and synthesis. Peptide binding in living organisms is quite labile which is associated with the presence of proteolytic enzymes. Therefore, to prevent protein hydrolysis, new, modified compounds are thought to mimic the properties and functions of peptide bond. These types of compounds are called peptidomimetics. In this monograph, we will focus on the biologically active fluorinated peptidomimetics, in which the amide bond has been replaced by a fluorinated group and thus they can "mimic" peptide bond functions (pseudopeptides). Other peptidomimetics with typical amide bond, but in which the remaining part of the molecule has been modified by introducing a fluorinated group or fluorine (peptide analogs) will also be discussed. The main goal of this work, however, is to demonstrate the beneficial effect of fluorine on the properties of the modified compounds and associated with it consequences. The superior goal of this work, however, is to demonstrate the unique effect of fluorine on the properties of the target compounds and in the design of higher order structures reflecting a more sophisticated molecular construction that broadens biological mimesis.

6

Kwas cykoriowy i jego właściwości lecznicze

Choińska Renata, Zawadzka Małgorzata, Golonko Aleksandra, Świsłocka Renata, Lewandowski Włodzimierz

Przemysł Chemiczny

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2020

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T. 99, nr 8

1210--1214

PL

Kwas cykoriowy to naturalny kwas fenolowy, stosowany jako nutrauceutyczny składnik żywności w związku z wykazywanym działaniem prozdrowotnym o charakterze przeciwutleniającym, przeciwwirusowym, przeciwnowotworowym, przeciwzapalnym, przeciwcukrzycowym oraz przeciwmiażdżycowym. Zdolność do dezaktywacji wolnych rodników, generowanych w nadmiernych ilościach w komórkach w odpowiedzi na niekorzystne czynniki środowiskowe i niewłaściwą dietę, jest kluczową jego cechą, określającą potencjał aplikacyjny. W celu zwiększenia efektywności antyutleniającej zaproponowano m.in. zmiany w strukturze elektronowej cząsteczki kwasu poprzez tworzenie kompleksów z nietoksycznymi metalami. Dokonano przeglądu właściwości kwasu cykoriowego i oceny dotychczas przeprowadzonych prób mających na celu zwiększenie aktywności antyutleniającej poprzez poprawę biodostępności.

EN

A review, with 61 refs., of curative properties of chicory acid and its derivatives esp. metal complexes.

7

Tridentate hydrazido-hydrazones vanadium complexes. Synthesis, properties and biological activity

Szklarzewicz Janusz, Jurowska Anna, Hodorowicz Maciej, Matoga Dariusz, Gryboś Ryszard, Filipek Barbara, Sapa Jacek, Głuch-Lutwin Monika, Mordyl Barbara, Kazek Grzegorz

Science, Technology and Innovation

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2019

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Vol. 4, no. 1

9--20

EN

Nine new vanadium complexes, with tridentate Schiff base ligand based on 3,5-di-tertbutyl-2-hydroxybenzaldehyde and different hydrazides, are described and characterized. The X-ray crystal structure of complex 8 shows distorted octahedral geometry of vanadium, with ONO ligand in equatorial position. The tridentate Schiff base ligand forms six membered and five-membered chelate rings at the V(V) acceptor center, with the corresponding bite angles being 82.97(9)˚ and 74.48(9)˚. The molecules are gathered by means of intermolecular OH...N hydrogen bond and layered by π...π interactions involving the pyridine and phenolate rings. Such interactions expand the structure along the crystallographic a axis. The complexes were characterized by the elemental analyses, IR, UV-Vis, EPR spectroscopy, cyclic voltammetry, thermogravimetry and magnetic susceptibility measurements. The stabilization role of co-ligands is discussed. The cytotoxicity versus HepG2 hepatocytes and inhibition of human recombinant PTP1B was studied.

8

Tiosemikarbazony : właściwości koordynacyjne w aspekcie aktywności biologicznej

Ostrowska M., Toporivska Y., Pyrkosz-Bulska M., Gumienna-Kontecka E.

Wiadomości Chemiczne

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2018

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[Z] 72, 7-8

449--467

EN

Thiosemicarbazones are considered to be potential therapeutics, because they possess a broad range of biological properties including antitumor, antimalarial and antimicrobial activity. Generally, the tiosemicarbazones coordinate to the metal centre by means of an (N,S) bidentate mode, and when an additional coordinating group is present, more diversified binding modes can occur such as a tridentate (X,N,S) coordination fashion. The stability of the metal complexes formed with the tiosemicarbazoness strongly depends on the character of the metal ion, the X-donor atom of the additional functional group and the position and type of the substituents at the tiosemicarbazones. The most prominent representative of this family is the α(N)-heterocyclic Triapine (3-aminopyridine- 2-carbaldehyde thiosemicarbazone; 3-AP), which is currently undergoing different phase-I and -II clinical trials as an antitumor agent, and demonstrates promising activity. Triapine is a very strong inhibitor of ribonucleotide reductase, the rate determining enzyme in the supply of deoxyribonucleotides for DNA synthesis required for cell proliferation. The mechanism of action involves most probably the formation of an iron(II)–Triapine complex, which reacts with molecular oxygen to result in the generation of reactive oxygen species. Subsequently, these reactive oxygen species are responsible for the quenching of the active-site tyrosyl radical of ribonucleotide reductase required for the enzymatic activity. As a result, the coordination chemistry of iron complexes of tiosemicarbazones has been receiving considerable attention. This review describes the coordination chemistry of tiosemicarbazones, in particular analogs of Triapine. The coordination compounds of d-block elements are discussed with respect to their bonding and structures. Several of complexes are mononuclear, with distorted tetrahedral, square planar, square pyramid or octahedral as their common geometries. The metal-binding ability of STSC at physiological pH was compared and shown. Further, various biological applications with emphasis an anticancer activity of the ligands/complexes are discussed in brief so as to indicate the importance of ligands under consideration.

9

Terapeutyczny potencjał pochodnych izotiazolowych : wpływ struktury związku na aktywność

Jęśkowiak I., Mączyński M., Ryng S.

Wiadomości Chemiczne

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2018

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[Z] 72, 11-12

867--885

EN

Isothiazole derivatives are compounds with potentially interesting biological activity. The work on the isothiazole ring was successfully conducted by Machoń from the Department of Organic Chemistry at Wrocław Medical University. Machoń received an isothiazole derivative – Denotivirum, which is an original Polish drug. This compound has antiviral, anti-inflammatory and bacteriostatic activity against Staphylococcus aureus. Within the group of isothiazolpyrimidine derivatives, Machoń selected a compound with a very strong antitumor effect (IP-10). This combination has gone through a preclinical study. The high antitumor activity was confirmed by the Bethesda USA Research Center, which qualified him for clinical trials [1–5]. The aim of the study was to review and evaluate the latest scientific works in the field of isothiazole derivatives and, above all, the dependence of their structure on activity. The Chemical Abstracts Database and Reaxys, together with other sources of information, was searched using isothiazole keyword. As a result of the search, the majority of works describing isothiazole derivatives for the anticancer (Tab. 1), immunological among other anti-inflammatory, immunosuppressive (Tab. 2) and antiviral (Tabs 3 and 4) activity were selected. Some substances have been tested for antibacterial, antifungal, insecticidal, antiparasitic, analgesic, antidiabetic and neuroprotective properties (Tab. 5). Analyzed were only compounds containing the isothiazole ring, which are not belong to condensed heterocyclic compounds such as benzoisothiazoles, isothiazolpyridines or furoisothiazoles. In conclusion, the most interesting works presented herein illustrate a wide range of activities of isothiazole derivatives depending on their structure, which also extend the scope of biological research revealing previously barren activities of this group of compounds.

10

Farmakologiczna aktywność flawonoidów i aminoflawonów

Szeliga D., Korabik M., Ochocki J.

Wiadomości Chemiczne

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2018

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[Z] 72, 7-8

563--583

EN

Aminoflavones belong to a group of flavonoids, compounds commonly found in nature. Their pharmacological and biochemical effects include cytotoxic, antioxidant and antitumor properties. The studies have shown that complexes of aminoflavons with metal ions can be potential drugs and seem to be promising in the treatment of ovarian cancer, breast cancer, lung adenocarcinoma and melanoma. In addition aminoflavones have a lower cytotoxic activity towards healthy cells than another compounds. In the view of their wide pharmacological and biological actions, they seem to have great therapeutic potential.

11

Aktywność biologiczna modyfikownych nukleozydów. Część 2

Szlenkier M.

Wiadomości Chemiczne

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2018

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[Z] 72, 5-6

245--264

EN

Part II of the review describes biological activities of nucleosides modified in the position 2’ and/or 3’ of a sugar moiety including 2’- and/or 3’-deoxy, 2’,3’-dideoxydidehydro and 2’-β-C-methylated derivatives. Analogues with a changed configuration in the sugar residue and others sugar modifications will be a subject of the part III of the review. Together with the part I it would be a short but possibly comprehensive review of nucleosides’ biological activities. In the group of analogues modified in the position 2’ and/or 3’ of the sugar moiety the following derivatives among others are listed: AZT (zidovudine) – one of the key nucleoside reverse transcriptase inhibitors (NRTI), which are the core of highly active antiretroviral therapy (HAART) against virus HIV; didanosine (ddI) – another potent NRTI with medical importance; stavudine – FDA approved NRTI; zalcitabine – historically important NRTI, however, because of a high mitochondrial toxicity is no longer in use; puromycin – a wide spectrum antibiotic which causes premature chain termination during translation, isolated from Streptomyces alboniger; gemcitabine – chemotherapy medication developed by Eli Lilly and Company and used to treat ovarian, breast, pancreas, bladder cancer and non-small cell lung carcinoma; cordycepin – the most intriguing analogue extracted from Cordyceps sp. known to traditional Chinese medicine (TCM) for centuries, possessing multi-activity against different cancer types; cladribine – used in the treatment of chronic lymphocytic leukemia, cutaneous T-cell lymphoma, hairy cell leukemia and non-Hodgkin’s lymphomas; valopicitabine – a prodrug form of 2’-C-methylcytidine, which was a promising HCV treatment agent, however, it was held during clinical trials and finally sofosbuvir developed by M.J. Sofia from Pharmasset Inc.– a ProTide prodrug form of 2’-deoxy-2’-fluoro-β-C-methyluridine 5’-monosphate, which revolutionized HCV infection therapy.

12

Aktywność biologiczna modyfikownych nukleozydów. Część 1

Szlenkier M.

Wiadomości Chemiczne

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2018

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[Z] 72, 3-4

109--126

EN

Every year, hundreds of new nucleoside analogues are obtained in laboratories around the world. As early as in 1964, 3’-azidothymidine (AZT) was first synthesized, which turned out to be the main weapon in the fight against HIV viruses 20 years later. Part I of the review includes nucleosides possessing modifications in the base moiety or having other heterocyclic bases. Nucleosides modified in the sugar residue, because of a broad spectrum of examples, will be a subject of part II and III of the review. In the group of analogues modified in the base moiety the following derivatives among others are listed: 5-iodo-2’-deoxyuridine (IDU), E-5-(2- bromovinyl)-2’-deoxyuridine (BVDU), capecitabine – prodrug form of fluorouracil, 7-deazaadenosine, BCX4430 (immucillin-A) – 9-deazaadenosine derivative active against filoviruses such as Ebola virus (EBOV). In the group of nucleosides having a different heterocyclic base the following derivatives are listed: ribavirin (RBV) and its analogues – RBV triphosphate is an inhibitor of many viral enzymes involved in the replication cycle, mizoribine (MZB) – a naturally occurring nucleosidic immunosuppressor, 5-ethynyl-1-β-"-ribofuranosyl-imidazole-4-carboxamide (EICAR) which suppresses development of murine leukemia cell lines and has a broad spectrum of activity against RNA and DNA viruses. The C-nucleosides group includes e.g. oxazinomycin – a natural antibiotic with growth inhibitory properties against gram (+), gram (–) bacteria and sarcoma, and formycin A isolated from Streptomyces lavendulae, which has cytostatic and antiviral activity.

13

Aktywność biologiczna modyfikowanych nukleozydów. Część 3

Szlenkier M.

Wiadomości Chemiczne

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2018

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[Z] 72, 9-10

767--787

EN

Part III of the review devoted to biological activities of nucleoside derivatives presents a further description of analogues modified in the sugar residue with particular focus on those with altered configuration in the 2’ or 3’ position, e.g. cytarabine – an old anticancer chemotherapy agent used to treat acute myeloid leukemia, acute lymphoblastic leukemia, and non-Hodgkin’s lymphomas; fludarabine – derivative of vidarabine used as a drug in the treatment of chronic lymphocytic leukemia, and non-Hodgkin lymphomas; clofarabine – approved by the FDA in 2004, a new-generation second-line drug for recurrent acute myeloid leukemia; and fialuridine – examined as a potential therapeutic for the treatment of HBV infection, however, clinical trials ended tragically. In the last section of the review derivatives with other modifications in the sugar moiety are described – carbocyclic and acyclic analogues, l-nucleosides and 5’-modified nucleosides. Among others, very important modified nucleosides are listed e.g. acyclovir, ganciclovir, DHPA, tenofovir, cyclopentenylcytosine, entecavir, carbovir, abacavir, lamivudine, telbivudine and sinefungin VA. All parts together make a possibly complete and concise review, including the latest reports, the most important groups of modified nucleosides, and should be considered as a whole. In the context of the activities description, there are references to the important molecular targets, mechanisms of action, pharmacodynamics, pharmacokinetics, toxicity, resistance, in vitro and in vivo tests or prodrug strategies, which can be a starting point for further study for chemists interested in medicinal chemistry.

14

Dwa oblicza selenu. Wybrane aspekty aktywności biologicznej selenu

Golonko A., Matejczyk M.

Budownictwo i Inżynieria Środowiska

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2018

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Vol. 9, no. 2

65--74

PL

Badania ostatnich lat wskazują na bardzo cenne pod względem medycznym właściwości selenu. Zainteresowanie selenem wzrosło odkąd poznano metody jego oznaczania w materiale biologicznym i jego rolę w organizmach żywych. Selen w zależności od stężenia wykazuje właściwości antyoksydacyjne i prooksydacyjne. Ponadto w badaniach na zwierzętach oraz ludzkich i zwierzęcych liniach komórkowych wykazuje właściwości antynowotworowe. W dobie wzrostu zachorowalności na choroby nowotworowe, selen cieszy się dużym zainteresowaniem naukowców na całym świecie. Obecne wyniki badań wskazują na bardzo różnorodną aktywność biologiczną selenu. Jednym z głównych mechanizmów działania tego pierwiastka jest czynny udział w ochronie komórek przed skutkami stresu oksydacyjnego. W prezentowanej pracy przeglądowej omówiono ogólne właściwości selenu, zaprezentowano jego aktywność biologiczną i obecny stan wiedzy o jego potencjalnym działaniu antynowotworowym. Przedstawiono mechanizmy działania selenu na poziomie molekularnym.

EN

Studies of recent years indicate the very valuable properties of selenium in medical field. The interest in selenium has increased since we learned the methods of its determination in biological samples and its role in living organisms. Selenium, depending on the concentration, has antioxidant and prooxidative properties. In addition, in animal studies and human and animal cell lines, it exhibits anti-cancer properties. In the era of increased incidence of human and animal cancer, selenium is very popular among scientists around the world due to its high biological activity. Current research results highlight the various effects of selenium molecular activity. One of the main mechanisms of action of this element is active participation in the protection of cells against the effects of oxidative stress. The review presents the general properties of selenium, its biological activity and the current state of knowledge about its potential anticancer activity. Also, known molecular mechanisms of selenium activity in a living cell are mentioned.

15

Application and properties of selected flavanones

Błazińska P., Sykuła A.

Biotechnology and Food Science

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2018

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Vol. 82, nr 1

61--74

EN

Flavanones, secondary plant metabolites, are one of the main group of flavanoids. They are widely spread in nature in many plants. The large diversity of structural structure of flavanones and controlled methods of modifying their molecules have a huge impact on biological activity. The present review will summarize the current knowledge about occurrence, obtaining by chemical synthesis, application and bioactivity of flavanones. Also, they are received from specific chemical synthesis. Flavanones have a great biological activity. Derivatives of flavanone have many different properties such as anti-inflammatory, anticancer, antioxidant, antimicrobial or hepatoprotective activities. These natural polyphenolic compounds are used in cosmetology, pharmacy and medicine. The demand and usage on them increases.

16

Tautomeryzm i aktywność biologiczna β-diketonów, triketonów, β-ketoestrów i β-ketoamidów : mini przegląd

Hansen P. E.

Wiadomości Chemiczne

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2017

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[Z] 71, 7-8

427--446

EN

The review deals with β-diketones, β-ketoester, β-ketoamides, triketones, their tautomerism and biological activity. In addition, it covers briefly methods to detect tautomerism in particular NMR and deuterium isotope effects on chemical shifts, both primary and secondary. A number of typical systems are treated such as: usnic acid, tetracyclines, piroxicam, curcurmines, humulones, acyltetramic acids and quinolone 3-esters.

17

Nukleozydy 8-azapurynowe : synteza i aktywność biologiczna

Głowacka I. E., Zdzienicka A.

Wiadomości Chemiczne

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2017

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[Z] 71, 3-4

147--174

EN

The synthetic approaches to 8-azapurine nucleosides and their biological activities have been reviewed. This class of compounds could serve as antimetabolites of purine nucleoside with potential clinical applications [1–6]. They were primarily synthesized by glycosylation of 8-azapurines, which could be easily prepared from appropriately substituted 4,5-diaminopyrimidines when reacted with nitric(III) acid [1]. Since in 8-azapurines at least three nitrogen atoms could serve as nucleophilic centers the regiochemistry of glycosylation was discussed in details. Generally, mixtures of N9, N8 and N7-substituted 8-azapurine nucleosides were formed when reactions were carried out at room temperature (kinetic control), while N9-substituted analogs were produced at elevated temperatures (thermodynamic control). On the other hand, no differences in the stereochemical outcome of glycosylation were noticed for canonical purine nucleobases and their 8-aza analogues since ratios of α and β anomers appeared to be closely related to the structure of a sugar component. Multidirectional biological activities of 8-azapurines and their nucleosides, including antitumor, antiviral and antibacterial, were presented for the most acclaimed examples. However, none of these compounds was approved as a drug. The current interest in 8-azapurines and their nucleosides takes advantage of a significant fluorescence (opposite to purines), which was found to be a pH-dependent thus providing an excellent tool for advanced studies in nucleic acid chemistry.

18

Naturalne i syntetyczne pochodne 5,8-chinolinodionu wykazujące aktywność biologiczną

Kadela-Tomanek M., Chrobak E., Bębenek E., Boryczka S.

Wiadomości Chemiczne

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2017

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[Z] 71, 11-12

795--815

EN

The compounds produced by a living organisms are most commonly used as medicinal agents and starting materials to the preparation of new semi-synthetic derivatives. It is estimated that over 23% of currently used medicinal products are natural substances. Natural compounds and their semisynthetic derivatives are most often used in the treatment of cancer and the treatment of infectious diseases. One of the groups of compounds obtained from Gram-positive bacterium are 5,8-quinolinedione antibiotics, like: streptonigrin, lavendamycin and streptonigron. The all compounds exhibit high anticancer, antimicrobial and antiviral activity. Unfortunately due to high toxicity this alkaloids did not find place in the therapy. The mechanism of action depends on interaction of compounds with the nicotinamide quinone oxidoreductase 1 (NQO1). The 5,8-quinolinedione can be reduced by the NAD(P)H as a cofactor to form the semiquinone or hydroquinone intermediates. These compounds can react with oxygen yielding a regenerated 5,8-quinolinedione fragment and creating the hydroxyl radicals, which are ultimately responsible for the DNA strands cleavage. The structure–activity relationship study has shown that the most important part of the molecule is the 5,8-quinolinedione moiety. Furthermore, it was found, that the introduction of amine, hydroxyl or thiol substituents at position 6 or 7 of the 5,8-quinolinedione moiety results in an enhanced biological activity. A lot of synthetic derivatives of 5,8-quinolinediones which containing amine, alkoxyl and thiol groups at the C-6 or/and C-7 positions have been obtained during the last few years. Commonly this compounds are obtained in the reaction of 6,7-dichloro-5,8-quinolinedione with nucleophilic factor. Depending on the reaction conditions, mono- or di-substituted derivatives are obtained. Most of synthesized compounds exhibit high biological activity, like: anticancer, antibacterial, antiviral, anti-inflammatory.

19

Synteza i aktywność biologiczna pochodnych pirolo[2,3-d]pirydazyny

Redzicka A., Tylińska B.

Wiadomości Chemiczne

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2016

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[Z] 70, 3-4

141--161

EN

Pyrrolo[2,3-d]pyridazines are one of the four structural isomers of the bicyclic ring system containing pyrrole moiety condensed with a pyridazine ring. This review presents most of the literature data about synthetic pyrrolo[2,3-d]pyridazine derivatives and their biological activity. These 5,6-diazaindole analogues were first synthesized by Fischer et. al. in 1928. Compounds containing the pyrrolo[2,3-d] pyridazine scaffold can be synthesized from different substrates, but the syntheses may be classified into two main categories: annulation of pyrrole ring on to pyridazine derivatives or annulation of pyridazine ring on to pyrrole derivatives. Pyrrolo[2,3-d]pyridazine derivatives have attracted considerable interest, owing to diverse biological activities. Most of them have been studied as antitumor and antiviral. Pyrrolo[2,3-d]pyridazines can also be used as acid pump antagonist.

20

1’-homonukleoz(t)ydy : synteza i aktywność biologiczna

Gotkowska J., Piotrowska D. G.

Wiadomości Chemiczne

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2016

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[Z] 70, 5-6

319--351

EN

Long-lasting interest in the synthesis of nucleos(t)ide analogues is dictated by hope to obtain compounds possessing antibacterial, antiviral and antitumor activities [1, 2]. Introduction of a methylene linker between an anomeric carbon and the nucleobase nitrogen atom produces a new class of compounds called 1’-homonucleos(t)ides as potentially active analogues. Although a sugar ring in nucleosides can be replaced by several cyclic or even acyclic moieties we focus attention on compounds containing the tetrahydrofuran ring. Since methods of attachment of nucleobases are limited to their alkylation with appropriate compounds and the de novo synthesis we discussed various synthetic approaches to substituted tetrahydrofuranes in racemic or optically pure forms. Various pentose and hexose derivatives were employed as starting materials and their transformations into the final sugar frameworks were detailed, thus revealing the importance of these class of compounds. To prepare deoxysugars Barton-McCombie reaction sequence was applied. A significant number of final 1’-homonucleos(t)ides were screened for antiviral and cytotoxic activity to identify a few very potent compounds. Thus, phosphonates trans- and cis-138a were as active against HCMV as ganciclovir. In addition trans- -138a inhibited the proliferation of several murine and human cancer cell lines with IC50s in the μM range. 1’-Homonucleosides 64b and 66b exhibited selective antiviral activity against HSV-1 TK– and HSV-2 TK– (MIC = 8–12 μg/mL). Compound 129 was found active against HCV (EC = 6.31 μM) and reduced growth of CCRF-CEM cells with IC50 = 5.73 μM. Despite limited activity observed so far for the known 1’-homonucleos( t)ides and their analogues, they deserve further interest both from the synthetic point of view and biological potential inherent in molecules having nucleobase scaffolds.