Wyniki wyszukiwania - BazTech

1

Zastosowanie związków kompleksowych platyny, palladu i kobaltu w medycynie. Cz. 1

Pawlak Marta, Drzeżdżon Joanna, Jacewicz Dagmara

Wiadomości Chemiczne

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2020

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[Z] 74, 11-12

797--822

EN

The complex compounds containing metal ions are a group of compounds widely used in medicine. More and more metals are also being used to create cancer drugs or to help with other very serious diseases. Anticancer drugs are a particular use of complex compounds. Many thousands of platinum(II) compounds have been synthesized in cancer therapy, but only six of them have found use in the treatment of cancer. The most popular and the most commonly used compound is cisplatin, it has become the basis for the treatment of bladder, cervical, head, esophagus and many cancers occurring in children. The mechanism of action of platinum(II) and platinum(IV) compounds against cancer cells is to inhibit DNA replication, then RNA transcription and stop the G2 phase of the cell cycle and lead to programmed cell death or apoptosis. Coordination compounds containing more than one metal ion in their composition open new possibilities in the fight against cancer. Pt-DNA connections created by compounds containing at least two metal atoms are different from those formed by cisplatin. The basic dinuclear structure allows for great flexibility in forming DNA-DNA or DNA-protein bonds. The cobalt(III) complexes began to be used to image areas of hypoxia in cancer cells. It is believed, that cobalt(III) complexes undergo bioreduction, which leads to the release of the labile cobalt(II) complex and one or more bioactive ligands. Studies on nitro-Co(III) complexes containing acetylacetone and a nitrogen mustard ligand have shown that it is a particularly effective anti-cancer drug. Due to the fact that many people have cancer new effective anti-cancer drugs with low toxicity and no side effects are still being sought.

2

Amigdalina : lek przeciwnowotworowy czy trucizna?

Jaszczak E., Narkowicz S., Namieśnik J., Polkowska Ż.

Analityka : nauka i praktyka

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2017

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nr 2

64--67

PL

Pomimo szerokiego zakresu możliwości waliki z chorobami nowotworowymi dzisiejsza medycyna nie jest wystraczająco skuteczna. Uzupełnieniem tradycyjnej terapii może być medycyna alternatywna, której przykładem jest leczenie amigdaliną.

3

Kompleksy kwercetyny z metalami jako potencjalne leki o aktywności przeciwnowotworowej : struktura, aktywność i biodostępność

Golonko A., Świsłocka R., Lewandowski W.

Przemysł Chemiczny

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2016

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T. 95, nr 9

1774--1780

PL

Brak uniwersalnych leków o aktywności przeciwnowotworowej powoduje, że obecnie wiele badań skupia się poszukiwaniu nowych związków chemicznych o aktywności antyoksydacyjnej i cytotoksycznej. W praktyce klinicznej stosuje się wiele terapeutyków, ale ich toksyczne działania uboczne, takie jak zahamowanie czynności szpiku zmuszają naukowców do syntezy leków o zredukowanym działaniu niepożądanym. Kwercetyna jest flawonoidem, który sam w sobie wykazuje aktywność przeciwnowotworową, a dodatkowo jej struktura umożliwia łatwe tworzenie związków chelatowych z metalami. Kompleksy związków bioaktywnych i jonów metali często wykazują silne właściwości cytotoksyczne i przeciwnowotworowe. Dokonano przeglądu literatury podsumowującej dotychczasowe badania aktywności biologicznej kompleksów kwercetyny z metalami na wybrane linie komórkowe.

EN

A review with 59 refs.

4

Drożdże piekarnicze Saccharomyces cerevisiae jako eukariotyczny organizm modelowy - cz. II

Cal-Bąkowska M.

Laboratorium - Przegląd Ogólnopolski

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2015

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nr 9-10

65--68

PL

Odpowiedź komórkowa na uszkodzenia DNA jest niezwykle podobna pomiędzy komórkami drożdży oraz wyższymi eukariontami. Drożdże Saccharomyces cerevisiae są użytecznym modelem w badaniach wielu molekularnych mechanizmów, w tym działania nowych chemioterapeutyków. Na modelu drożdżowym możliwe jest prowadzenie bardzo szczegółowych i ciekawych badań nad cyklem komórkowym.

EN

The cellular response to DNA damage is remarkably similar between the yeast cells and higher eukaryotes. The yeast Saccharomyces cerevisiae is a useful model to study many molecular mechanisms and also the mechanism of action of new chemotherapeutic agents. It is possible to carry out on yeast model detailed and interesting research of the cell cycle.

5

Zirconia nanoparticles impact on morphophysiological data and mineral composition of P. ostreatus

Doroshkevich N. V., Frontasyeva M. V., Doroshkevich V. S., Lygina O. S., Shylo A. V., Ostrovnaya T. M., Pavlov S. S., Pirko N. N., Zelenyak T. Y., Konstantinova T. E., Lyubchyk S. B., Doroshkevich A. S.

Ecological Chemistry and Engineering. S

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2015

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Vol. 22, nr 2

169--188

EN

Neutron activation analysis of the Pleurotus ostreatus showed that adding of solid solution of ZrO2-Y2O3 hydroxide and oxide (3 mol % Y2O3) nanoparticles of size 4 and 9 nm at a concentration of 0.2 weight percent in a nutrient medium (Czapek) alters the character of physiological processes in the biological tissues of the mushrooms. This is manifested in the form of a significant change in morphological and physiological characteristics of the mushrooms and the elemental composition of the dry biomass. In particular, it is shown that the intercalation of nanoparticles into the tissues of the mushrooms leads to an increase of 1.3-1.4 times (more than 2.6 g/dm3) of biomass accumulation (industrial strain HK 35) and decrease of 1.7-1.8 times (below 1.7-2.5 mg/mm3) of concentrations of extracellular proteins into the culture fluid at a substantially constant value of the acidity. It is shown that the addition of ZrO2+3 mol % Y2O3 nanoparticles of sizes 4 or 9 nm into tissue of mushroom at step of the mother mycelium in very small concentrations can alter effectively the chemical composition of the substances produced by the cells and consequently, its physiological activity. It is shown that the use of low concentrations of ZrO2 nanoparticles allow to increase the yield and resistance of crops to diseases up to 1.2-1.5 times, as well as in the long term can be used in biomedical technologies for the treatment of cancer diseases.

PL

Zastosowanie neutronowej analizy aktywacyjnej w badaniach Pleurotus ostreatus pokazało, że dodawanie stałego roztworu wodorotlenku i tlenku ZrO2-Y2O3 (3 mol % Y2O3) w postaci nanocząstek o rozmiarze 4 i 9 nm w stężeniu 0,2% wagowych w pożywce (Czapek) zmienia charakter procesów fizjologicznych w tkankach biologicznych grzybów. Zjawisko to przejawia się w postaci znacznych zmian morfologicznych i fizjologicznych cech grzybów oraz składu pierwiastkowego suchej biomasy. W szczególności wykazano, że wprowadzenie nanocząstek do tkanek grzybów prowadzi do wzrostu 1,3-1,4 razy (więcej niż 2,6 g/dm3) akumulacji biomasy (szczep przemysłowy HK 35) i spadku o 1,7-1,8 razy (poniżej 1,7-2,5 mg/mm3) stężenia pozakomórkowych białek w płynie hodowli przy zasadniczo stałej wartości kwasowości. Pokazano, że dodanie ZrO2 + 3% mol nanocząstek Y2O3 rozmiarów 4 lub 9 nm do tkanki grzyba na etapie grzybni macierzystej, w bardzo małych stężeniach, może skutecznie zmieniać skład chemiczny substancji wytwarzanych przez komórki, a co za tym idzie, jej aktywność fizjologiczną. Wykazano, że stosowanie niskich stężeń nanocząstek ZrO2 zwiększa wydajności i podnosi odporności roślin na choroby do 1,2-1,5 raza, a także w przyszłości może być stosowane w technologii biomedycznej, w leczeniu chorób nowotworowych.

6

Syntezy wybranych leków pochodnych 2-amino-1H-benzimidazolu

Nowicka A., Nawrocka W. P.

Wiadomości Chemiczne

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2013

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[Z] 67, 7-8

695--714

EN

2-Amino-1H-benzimidazole fragment occurs in broad spectrum of drugs with anticancer, antiviral, antifungal, anthelmintic and antihistamine properties. There are 30 drugs, 2-amino-1H-benzimidazole derivatives, registered in the world. Mebendazole, Albendazole and another derivatives are antihelmintic drugs which are believed to work by selectively inhibiting the synthesis of microtubules in parasitic worms, and by destroying extant cytoplasmic microtubes in their intestinal [9, 12, 14]. Astemizole was a second-generation antihistamine drug that has a long duration of action. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects [19]. Mizolastine is non-sedating antihistamine drug [21]. It blocks H1 receptors and doesn’t prevent the actual release of histamine from mast cells, but just prevents it binding to receptors. Enviroksim and its isomer Zinviroksim and Enviraden are antivirial drugs [26, 27]. They inhibit multiplication of 15 different serotypes of rhinovirus. Benomyl is a systemic fungicide that is selectively toxic to microorganisms [29]. Benomyl binds to microtubules, interfering with cell functions, such as meiosis and intracellular transportation. Carbendazim is a widely used, broad-spectrum fungicide and a metabolite of Benomyl [29]. It’s also shown an anticancer activity. Oncodazole shows antifungal, antineoplastic and antihelmintic activities, which exerts its effect in cells by binding to tubulin and interfering with the polymerization of microtubules [33].

7

Chemiczne aspekty celowanej terapii przeciwnowotworowej II. Połączenia nośnik -lek

Werengowska K. M., Wiśniewski M., Terzyk A.P., Gurtowska N., Drewa T. A., Olkowska J.

Wiadomości Chemiczne

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2012

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[Z] 66, 7-8

637-670

EN

Traditional anticancer therapy is usually low effective. Popular and common drugs applied in anticancer therapy are characterized by low solubility and nonspecific biodistribution in an organism. The chemotherapy kills not only cancer but also healthy cells [4]. Building of modern drug delivery systems based on nanocarriers is a new method of anticancer treatment. The present study is directed towards nanomaterials (as carbon nanotubes, liposomes, polymeric micelles) as modern drug carriers. Thus, we characterized mechanisms of actions of traditional chemotherapeutics: paclitaxel, cisplatin and doxorubicin (Figs. 3–5) [1, 15, 21]. The purpose of this study is a description of the bioconjugation of drug-nanocarrier. Chemotherapeutics can be connected to external or internal surfaces of nanocarriers (Fig. 6) [6]. We described two main methods of drug delivery from internal space of nanocarriers: nanoextraction and nanocondensation (Fig. 7) [32]. The type of drug-carrier bonding can be covalent or noncovalent. We report recent advances in the field showing the formation of esters (Figs. 10–11) [28, 29, 53, 54], acethylhydrazone (Fig. 12) [55–61], amides [62–64], and disulfides groups [12, 65]. These reactions depend on functional groups in structures of drugs and require suitable modification of nanocarrier surfaces. In practice, the functionalization of nanocarrier surface is associated with the covering with polymers including PE G, HPMA, PG and PL GA [3]. Adsorption is the most popular process of bonding chemotherapeutic and nanomaterials (Fig. 13) [66]. Special attention is paid to electrostatic interaction between drugs: paclitaxel [74], cisplatin [59, 76, 77], doxorubicin [67–73] and nanocarriers: carbon nanotubes and/or polymeric micells. By application of modern anticancer therapy, drugs are preserved from lysosomal degradation and to fast reaction in biological environment. Finally, nanocarriers improve adsorption of drug and increase concentration of drug only in cancer tissues [6, 7].

8

Synteza izoprenoidowych fosfolipidów

Biodrowska K., Draus A. W., Gliszczyńska A., Gładkowski W., Leśniak A., Wawrzeńczyk C.

Przemysł Chemiczny

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2012

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T. 91, nr 5

692-696

PL

Otrzymano cztery nowe 1,2-diacylofosfatydylocholiny z resztami acylowymi kwasów izoprenoidowych w pozycji sn-2. 1-Palmitoilo-sn-glicero-3-fosfocholinę estryfikowano kwasami: geranylowym, (E)-3,7-dimetylookt-4-enowym, (2E, 8E)-3,7,11-trimetylododeka-2,8-dienowym oraz (4E, 8Z)-5,9,13-trimetylotetradeka- -4,8,12-trienowym w obecności N,N’-dicykloheksylokarbodiimidu (DCC) i 4-dimetyloaminopirydyny (DMAP). Otrzymane fosfolipidy będą poddane badaniom na aktywność cytotoksyczną w stosunku do linii komórkowych nowotworów ludzkich, gdyż w świetle danych literaturowych mogą okazać się przydatne w terapii chorób nowotworowych.

EN

1-Palmitoyl-sn-glycero-3-phosphocholine was esterified with geranic, (E)-3,7-dimethyloct-4-enoic, (2E, 8E)-3,7,11- trimethyldodeca-2,8-dienoic and (4E, 8Z)-5,9,13-trimethyltetradeca-4,8,12-trienoic acids in presence of N,N’- dicyclohexylcarbodiimide and 4-dimethylaminopyridine to prep. 4 resp. new 1,2-diacylphosphatidylcholines with isoprenoid residues in sn-2 position as prospective anticancer agents.

9

Bisinterkalatory jako potencjalne leki przeciwnowotworowe

Stańczak A., Szumilak M.

Wiadomości Chemiczne

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2009

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[Z] 63, 9-10

847-875

EN

Intercalators constitute a group of compounds which interact reversibly with DNA double helix. The insertion of planar, polycyclic aromatic systems between adjacent base pairs leads to topological changes in the double helix (lengthening, unwinding) and disrupts replication, transcription and repair processes [1–4]. Some of the monointercalators e.g. doxorubicin are valuable drugs, but their clinical effectiveness is limited by their undesirable side effects, and development of multidrug resistance [12]. In order to overcome these limitations bisintercalators have been designed. Dimerization of monointercalating compounds was supposed to enhance their anticancer activity and minimize side effects [1,7]. Many research groups have been interested in designing various groups of bisintercalating agents of diverse chemical structure and biological properties, such as echinomycin antibiotics [5, 7–10], 7H-pyridocarbazole derivatives [19–21], bisanthracyclines [7, 12, 16], bisnaphthalimides [7, 22–37], bisacridines [38–48] and bisimidazoacridones [50–52]. There have been a number of modifications undertaken on polyaromatic rings, and linker chains in an attempt to improve the compounds’ activity. The structure-activity relationships have been suggested. It has been discovered that introduction of small lipophilic substituents or additional heterocycles into ring systems may lead to significant changes in binding affinity and cytotoxic activity of the compounds. It was discovered that many tumor types contained elevated polyamine levels and an active polyamine transporter for importing exogenous polyamines. Designing bisintercalators with aminoalkyl chains similar to polyamines has given a chance to improve selectivity in drug delivery to rapidly proliferating cells by utilizing the polyamine transporter. More extensive SAR studies revealed significant influence of length and rigidity of a linker binding two intercalating moieties on binding affinity and antiproliferative activity of bisintercalators. Intercalation and topoisomerases inhibition are not the only possible modes of action of the compounds. Some of them exert cytotoxic effect through induction of apoptosis e. g. bisnaphthalimidopropylspermidine (BNIPSpd, (29) Fig. 9) or disrupting repair process of DNA double helix (WMC -26, (55) Fig. 18). In this work we presented enormous chemical diversity of bisintercalators and depicted multiplicity of structural modification of dimeric molecules which may lead to enhanced cytotoxic activity becoming valuable anticancer drugs.

10

Rola hipoksji w postepach w diagnostyce i terapii chorób nowotworowych

Błaszczak-Świątkiewicz K., Mikiciuk-Olasik E.

Wiadomości Chemiczne

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2008

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[Z] 62, 11-12

1065-1089

EN

Contemporary radiopharmacy has played a significant role in the development of early oncological diagnostics. Such radiopharmaceutics as 18F-FMISO, 123I-IAZA, 99m Tc-HL-91 (Fig. 1b, 3b, 7b) are used in the state-of-the art scintigraphic and tomographic techniques, i.e. in the PET and SPECT methods to determine carcinoma progression and detect cells in hipoxic state already at the early stage of carcinoma development [2, 3]. These noninvasive and selective for hipoxic cells methods are characterized by excellent sensitivity and do not exert noxious effect on the remaining cells of the human organism [4, 5]. Characteristic hipoxia of solid tumors can be also identified with invasive methods, e.g. Elisa test or measurement of oxygen concentration in pathological cells using a microprobe. However, medical interference in the tissues affects the condition of the whole organism. Technical complications and low accuracy resulting from non-uniform hipoxia of the cancerous tissue environment render rear usage of these methods in clinical practice [3]. Diagnosis of hipoxia occurring in the carcinoma-changed cells permits treatment with drugs possessing bioreductive mechanism of activity. In this group of drugs, apart from nitro compounds and chinon derivatives, we can distinguish compounds with N-oxide structure [25]. Tripazamine (Fig. 11b) and banoxantrone (Fig. 11a) represent the latter group of compounds. These are so far the drugs with the best therapeutic parameters expressed by selectivity, efficiency of action and low general toxicity [25]. Also, gene therapy with the use of adenovirus vector coding nitroreductase seems to be a promising mode of treatment. This enzyme induces cytotoxic activity of nitro compounds, e.g. CB1954 (Fig. 10c), for cancerous cells with hypoxia [26].

11

Nowa synteza leku przeciwnowotworowego - docetakselu

Michalak O., Bańkowski K., Achmatowicz O.

Przemysł Chemiczny

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2007

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T. 86, nr 8

783-788

12

Indolochinoliny : syntezy nowych analogów

Badowska-Rosłonek K., Łuniewski W., Ciesielska A., Kaczmarek Ł.

Przemysł Chemiczny

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2006

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T. 85, nr 5

314-320

PL

Przedstawiono przegląd prac badawczych Instytutu Farmaceutycznego w zakresie poszukiwania nowych leków przeciwnowotworowych z grupy indolochinolin.

EN

A review with 35 refs. covering the Pharmaceutical Research Inst. (Warsaw) works on prepn. of new indolo[2,3b]quinoline derivs. based on biol. (in)active indolequinoline pharmacophores, their cytotoxic properties, and their structure–activity relationships. Two main groups are glycosides or indoloquinolines with aminoalkyl side chains connected with the aromatic moiety through various functions.

13

Anastrozol : nowa metoda syntezy

Chojecka-Koryn E., Zagrodzki B.

Przemysł Chemiczny

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2006

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T. 85, nr 5

338-341

PL

Anastrozol – selektywny, niesteroidowy inhibitor aromatazy stosuje się w lecznictwie jako lek pierwszej linii w leczeniu hormonozależnego raka sutka u kobiet po menopauzie. Celem prac prowadzonych w Instytucie Farmaceutycznym było opracowanie technologii produkcji anastrozolu, a także wytworzenie substancji czynnej, odpowiadającej wymaganiom pozwalającym na wykorzystanie jej do badań nad postacią leku. Opracowana technologia w pełni potwierdziła swą przydatność będąc podstawą do opracowania i wdrożenia zwalidowanego procesu wytwarzania anastrozolu w skali ćwierćtechnicznej.

EN

Anastrozole is a selective aromatase inhibitor, highly effective for the treatment of advanced breast cancer in postmenopausal women. Technological process for the anastrozole preparation had been developed in the Pharmaceutical Research Institute. The synthesis of Anastrozole was carried out according to the few-step synthetic route. Process validation was performed during the preparation of three production scale batches, and fully evaluated. The requirements for anastrozole quality and specification limits are concordant with the Pharmacopoeia requirements for the active substances.