Wyniki wyszukiwania - BazTech

1

Nienukleozydowe inhibitory odwrotnej transkryptazy HIV

Orzeszko A.

Wiadomości Chemiczne

|

2008

|

[Z] 62, 3-4

297-314

EN

This review attempts to briefly summarise the developments in anti-HIV therapy. The main attention was paid to the inhibitors of the virus enzyme reverse transcriptase (RT). Until 1987, no anti-HIV drug has been available, but an understanding of life cycle of HIV has led to an identification of several possible drug targets. At present, most drugs that have been developed act against the viral enzymes: reverse transcriptase, protease, as well as integrase. However, a serious problem with HIV treatment is that the virus undergoes mutations extremely easy. This results in rapid resistance to antiviral drugs. Non-nucleoside reverse transcriptase inhibitors (NNRTI's) have, in addition to the nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and fusion inhibitors, gained a definite position in the treatment of HIV-1 infection. To date three NNRTIs: Nevirapine, Delaviridine and Efavirenz have been approved by the US Food and Drug Administration for clinical use [3-8]. NNRTIs snugly fit into a specific allosteric "pocket", located at some 10 A* from the catalytic site, of HIV-1 RT and thus disrupt its enzymatic activity [5-7, 17, 18]. Several studies have revealed a common mode of binding for chemically diverse compounds with their target site at the RT [5]. The inhibitors cause a repositioning of the three-stranded sheet in the p66 subunit containing the catalytic aspartic acid residues 110, 185 and 186. This suggests that NNRTIs inhibit HIV-1 RT by locking the active catalytic site in an inactive conformation. When bound into their pocket at the HIV-1 RT, the inhibitors maintain a very similar "butterfly-like" conformation. They roughly overlay each other in the binding pocket and appear to function as ?-electron donors to aromatic side-chain residues surrounding the pocket [5]. Drug resistance is a key failure for treatment of HIV infection. The torsional flexibility of the inhibitors can generate numerous conformational variants and the compactness of the inhibitors permits significant repositioning and reorientation within the pocket. So, in this perspective, various new prototypes of NNRTI's were reported as potential lead compounds [20]. For example, Capravirine, Dapivirine as well as thiazolidinones belong to this group [24-29].

2

Estroimidowe materiały ciekłokrystaliczne

Orzeszko A.

Wiadomości Chemiczne

|

2005

|

[Z] 59, 3-4

231--248

EN

The credit for the discovery of liquid crystals must go to F. Reinitzer who in a paper submitted on May, 1888 described his observations of the colored phenomena occurring in melts of cholesteryl benzoate. He noted the "double melting" behavior in this case, whereby the crystals transformed at 145,5°C into a cloudy fluid, which suddenly clarified only on heating to 178°C. Mesophases are a state of order between crystals and liquids. They have imperfect long range orders of orientation and/or position. Thus, they can be fluid like a liquid and they can have anisotropic properties like crystals. The liquid crystals have a predominating orientational order. Despite intensive research activities of numerous research groups on polymers no systematic study on liquid crystalline polyimides had been published before 1985. Only two patents of Du Pont filed in 1979 reported on LC poly(ester imide)s. The fundamental study on this area was made by Kricheldorf. He found that the most promising substrate for synthesis of liquid crystalline poly(ester imide)s was trimellitic anhydride. It forms imide ester mesogenic group in main polymer chain. On the other hand it has been found that isolated phthalimide moiety not favor liquid crystalline order but connected with ester groups increases a possibility of forming mesophase. Low molecular weight cholesteric ester imides with oxyethylene spacers form liquid crystal SmA2 phase. It is possible due to microsegregation of hydrophobic parts of molecules. Similar compounds with polymethylene spacers exhibit monolayer SmA phase. In this case microsegregation is impossible. Also ester imides based on biphenyl mesogenic moiety show termotropic behavior. Cyanobiphenyl derivatives of such trimellitimides form a partially bilayered smectic Ad phase for the homologues with long N-alkyl substituents. The monolayer smectic A1 phase was observed for all members of 4'-undecyloxybiphenyl derivative series while the longer homologues exhibited SmA-SmC dimorphism. The reaction of imide compounds with Lawesson's reagent leads to monothio- and dithioimides, respectively. Liquid crystalline ester thioimides were obtained at first time by Orzeszko and Białecka. An incorporation of one or two sulfur atoms into an imide ring results in reduction of phase transition temperature values. This is a consequence of the considerable change of compound polarity and the increase of the molecular breadth.

3

Wybrane bioaktywne pochodne adamantanu

Orzeszko A.

Wiadomości Chemiczne

|

2004

|

[Z] 58, 7-8

599--612

EN

In 1933 adamantane was isolated from petroleum of Czechoslovakia by Landa [2]. Its unique structure is reflected in highly unusual physical and chemical properties. For example this hydrocarbon has extraordinary high melting point 269oC. It was also shown that the bromination is an ionic process; it is catalyzed by Lewis acids and not by peroxides or light. Adamantane possesses a unique rigid, but strain-free ring system, composed of three fused chair cyclohexane rings. The other source of adamantane derivatives are organic syntheses including cyclization and rearrangement of hydrocarbons. Also, it was found that 1-adamantanol refluxed with trifluoroacetic acid and respective heterocycles yielded N-adamantylated compounds [6]. Particularly the biological properties of adamantane derivatives are very interesting. The most known of clinical use is the antiviral drug 1-amnoadamantane (amantadine) [7-11]. In the presented paper only antimicrobial, antiviral as well as anticancer agents are described. Novel ester imides synthesised from trimellitic acid chloride and 1-adamantanol, 2-adamantanol, 1-adamantanemethanol or 1-adamantaneethanol, were tested as antimicrobial compounds [16-18]. Some of these derivatives showed significant activity. The incorporation of L-alanine and L-phenylalanine aw well as ?-amino acids into the phthalimide moiety as N-substituents, leads to strong antimicrobial activity against Staphylococcus aureus strains. A variety of 5'-N-phtaloyl-3'-azido-2',3'-dideoxythymidine derivatives has been synthesised and evaluated for their activity against HIV-1 and HIV-2 [28]. Most of the AZT derivatives showed antiviral activity in the lower micromolar concentration range. It should be notice that all these compounds were inactive against HIV in thymidine kinase-deficient cells, pointing to the compounds' requirement to release free AZT to afford antiviral efficacy. Tumor necrosis factor-alpha, so-called TNF-?, is a cytokine produced by numerous cell types among which monocytes/macrophages play a major role [29-40]. Investigation of the biological properties of TNF-?, in vitro as well as in vivo models, has revealed that this cytokine has both beneficial and unfavourable effects. In this context, it is interesting to search for new drugs working as stimulators or inhibitors of TNF-? production. It was found that N-(adamant-1-yl)monothiophthalimide and N-(adamant-2-yl)monothiophthal-imide showed over 200% enhancing of cytokine production, while some other imides were inhibitors. The known drug bropirimine is orally active immunomodulator that stimulates production of TNF-? and other cytokines and is now under phase II clinical trials for treatment of bladder carcinoma [43]. The inspiration for us was the search for bropirimine adamantane analogues [44]. The synthesis of adamantylated pyrimidines was based on the Traube reaction of 3-(adamantan-1-yl)-3-oxopropionic acid ethyl ester with urea, thiourea, guanidine as well as acetamidine, respectively. Then the compounds obtained were converted into respective bromo-, thio- and S-alkyl derivatives. The significant anticancer and antimicrobial properties of [2-(6-adamantan-1-yl-2-methylpyrimidin-4-ylsulfanyl)ethyl]dimethylamine were found.

4

Zastosowanie koagulacji objętościowej do podczyszczania ścieków z zakładów przemysłu tłuszczowego

Michel M. M., Orzeszko A.

Przegląd Naukowy Inżynieria i Kształtowanie Środowiska

|

2004

|

Vol. 13, No. 1

107--114

EN

For their primary treatment, in this paper, ten coagulants were used. The first examination was the so-called Jar-Test, by means of which the most potent agents i.e. Zetag 7635, Magnasol 5389 and PIX-113, respectively, were selected. Then, the efficiency of these coagulants in waste treatment was studied. Three main parameters: COD, amounts of hexane extractive substances and SO42-concentration were detenninate. It was found that the aforementioned coagulants reduced the COD parameter, as well as the amounts of dispersive greases and free fatty acids significantly. Unfortunately, the problem of the removal of sulfates remains still unsolved.

5

Sole Buntego - zapomniane związki

Orzeszko A., Kazimierczuk Z.

Wiadomości Chemiczne

|

1998

|

[Z] 52, 1-2

125-135

EN

This paper is devoted to organic thiosulfates, so called Bunte salts. On the occasion of the 150th anniversary of Hans Bunte's birth (1848), the short biographical note was annexed. The main, historical method of synthesis of organic thiosulfate was described with some novel modification [3-11]. In Figs 1 and 2 the general structure of Bunte salts and the mentioned reaction are shown, respectively. Newer methods of synthesis like, for example, the addition of thiosulfate anion to alkenes or oxiranes are presented in Figs 3 and 5 [2,12, 13, 18, 19]. In the next chapter some chemical properties of Bunte salts were described . Aqueous solutions of these compounds are unstable. In acid medium they hydrolyse to thiols, while in basic one to appropriate disulfides (Figs 6, 7) [3,10, 22-26]. The reaction of dihalides with sodium thiosulfate leads to 'double' Bunte salts carrying two thiosulfate end groups. It was found that in presence of NaOH or H2O2 these salts give appropriate polydisulfides [8, 9]. The scheme of this process is shown in Fig. 11. It was found that anodic oxidation of Bunte salts leads also to di - and polydisulfides [7]. Usually, organic sulphur compounds show strong biological activity. There are a few examples of biological studies on organic thiosulfates in the literature. The sodium ethylthiosulfate, originally prepared by Bunte [3], exhibits a striking synergistic affect with the bacteriostatic 2-mercaptobenzothiazole against Staphylococcus aureus and tubercle bacillus [43, 44]. Sodium salt of the aromatic 3-nitrophenylthiosulfate was reported to show strong preventive and curative activity against fowl coccidiosis [22]. Radioprotective properties of heterocyclic derivatives of thiosulfates were also investigated [48]. The chemical structure of Bunte salt anions carrying a long aliphatic chain suggests their amphiphilic character. It is known that amphiphility of numerous quaternary ammonium salts is responsible for their ability to damage cell membranes. We paid our attention to the relationship between the chemical structure and the antibacterial and fungicidal activity of a number of known and newely synthesised Bunte salts [7]. The results of this work are presented in Fig. 13. Many Bunte salts have excellent technical applications described in the patents cited [42-49].