Wyniki wyszukiwania - Biblioteka Nauki

1

Synthesis of 2-(4-Chloro-2-mercaptobenzenesulfonyl)-3,5-dihydroxy-1,1-dioxo-2H-1,2,4,6-thiatriazine Derivatives with Potential Anti-HIV and Anticancer Activities

100%

Brzozowski Z. , Sławiński J.

Polish Journal of Chemistry

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2007

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tom Vol. 81, nr 8

1419-1426

EN

Several 2-(4-chloro-2-mercapto-5-R-benzenesulfonyl)-3,4-dihydroxy-1,1-dioxo-2H- 1,2,4,6-thiatriazines (9–12) have been synthesized as potential anti-HIV (9–10) or anticancer (11–12) agents. The in vitro anti-HIV or antitumor activities were tested at theUSNational Cancer Institute (Bethesda,MD), and the structure-activity relationships are discussed. Compound 9 (R =Me) showed good anti-HIV activity with 50% effective concentration (EC50) value of 73.2 ěMand moderate cytotoxic effect (IC50= 220.0 miM). The compounds 11 and 12 exhibited high or reasonable activity against most (98%) of the human tumor cell lines tested. Compound 12 (R = 4-ClC6H4NHCO) is theprominent of the compounds due to its good activity against 54 human tumor cell lines (GI50 = 0.67–38.9 ěM), and remarkable selectivity toward renal cancer RXF 393 cell line (GI50 = 0.67 miM).

2

Molecular modeling of selected magnesium organic salts. Structure - activity relationship

100%

Marcoin W.

Journal of Elementology

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2005

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tom 10

|

nr 4 Suppl.1

67

3

AlfaVbeta3 Antagonists Based on a Central Benzoic Acid Scaffold

100%

Will D. , Breipohl G. , Gourvest J. , Ruxer J. , Doucet B. , Auberval M. , Baran R. , Gaillard M. , Gadek T. , Knolle J. , Stilz H. U. , Peyman A.

Polish Journal of Chemistry

|

2005

|

tom Vol. 79 / nr 3

567-572

EN

A series of novel, highly potent _v_3 antagonists based on a benzoic acid scaffold and containing an acylguanidine as an Arg-mimetic and sulfonamide side chains is described. The compounds are selective against the fibrinogen receptor _IIb_3 and they are capable of inhibiting bone resorption in vivo in a TPTX model of osteoporosis. Therefore the compounds are promising drug substances for the treatment of osteoporosis.

4

Structural studies of cysteine proteases and their inhibitors.

100%

Grzonka Z. , Jankowska E. , Kasprzykowski F. , Kasprzykowska R. , Łankiewicz L. , Wiczk W. , Wieczerzak E. , Ciarkowski J. , Drabik P. , Janowski R. , Kozak M. , Jaskólski M. , Grubb A.

Acta Biochimica Polonica

|

2001

|

tom 48

|

nr 1

1-20

EN

Cysteine proteases (CPs) are responsible for many biochemical processes occurring in living organisms and they have been implicated in the development and progression of several diseases that involve abnormal protein turnover. The activity of CPs is regulated among others by their specific inhibitors: cystatins. The main aim of this review is to discuss the structure-activity relationships of cysteine proteases and cystatins, as well as of some synthetic inhibitors of cysteine proteases structurally based on the binding fragments of cystatins.

5

Synthesis, structure activity relationship and mode of action of insect pheromones. A contribution to the problem of chemical information among insects

88%

Bestmann H. J. , Vostrowsky O.

Pestycydy

|

1990

|

nr 1

6

Syntheses of a New Series of N-Amino-N"-(benzenesulphonyl)guanidine Derivatives with Potential Antitumor Activity

88%

Sławiński J. , Bednarski P. , Grunert R. , Reszka P.

Polish Journal of Chemistry

|

2003

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tom Vol. 77 / nr 1

53-64

EN

Syntheses of novel N-amino-N_-(benzenesulphonyl)guanidines (4a-h, 5a-g) from N- (benzenesulphonyl)cyanamide potassium salt and hydrazine derivatives are described. Compounds 4b, 5a-c and 5e were evaluated by in vitro assays of growth inhibition against several human tumor cell lines. The highest in vitro cytotoxic activities were found for 3-phenylamino-1-(2-benzylthio-4-chloro-5-methylbenzenesulphonyl)guanidine (5b) (IC50 = 2.35-8.14 _M) and 3-phenylamino-1-(4-chloro-2-ethoxycarbonylmethylthio- 5-methylbenzenesulphonyl)guanidine (5c) (IC50 = 2.74-10.6 _M), while other tested compounds (5a, 5e) showed the moderate cytotoxic activities.The molecular orbital calculation of the possible tautomeric forms of the benzenesulphonylguanidine derivatives were also presented.

7

Synthesis, Biological, Immunological and Anticancer Properties of a New Brassinosteroid Ligand

88%

Swaczynova J. , Sisa M. , Hnilickova J. , Kohout J.

Polish Journal of Chemistry

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2006

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tom Vol. 80, nr 4

629-635

EN

We have developed polyclonal antibodies against the brassinosteroid, 24-epicastasterone. Antiserum against this substance was produced by immunizing rabbits and mice with 24-epicastasterone O-(carboxymethyl)oxime (24-epiCS-CMO) conjugated with bovine-serum albumin (BSA). The conjugates were prepared by a mixed anhydride procedure. The antibodies obtained were tested in enzyme-linked immunosorbent assay (ELISA) using 24-epiCS-CMO-peroxidase conjugate. The use of the ELISAallowed detection over the range of 0.01 to 500 pmoles. Natural brassinosteroids (BRs) like brassinolide, and 24-epibrassinolide exhibited relatively high cross-reactivities but many other natural BRs were inactive. The 24-epiCS-CMO ligand was also slightly active in second bean internode bioasaay and on cancer cell lines of different histopathological origin.

8

Review of methods applied to search structure-activity relationship

88%

Wilkowska E. , Golebiewski W. M.

Pestycydy

|

2001

|

nr 1-2

9

Kompleksy platyny (IV) jako potencjalne związki przeciwnowotworowe

75%

Ciołkowski M. , Budzisz E.

Wiadomości Chemiczne

|

2007

|

tom [Z] 61, 1-2

43-60

EN

Cisplatin is an important anticancer drug. Unfortunately it does not bring satisfactory effects in all types of tumor. Other problems are its toxicity and intrinsic or acquired resistance of tumor cells. That is why new drugs based on this molecule are being searched. One of the promising group of chemical compounds are neutral platinum(IV) complexes. They are more inert than platinum(II) complexes. In consequence their reactivity in bloodstream is weaker and more molecules can reach their target. Many studies were done to establish the relation among the structure, lipophilicity, reduction potential and cytotoxicity of those complexes. It is believed that platinum(IV) complexes must be reduced to platinum(II) complexes to obtain cytotoxicity. The speed of reduction depends on the nature of axial ligands. The complexes with chloride ligands are reduced the most quickly and complexes with hydroxide ligands are reduced the most slowly. In vitro cytotoxic activity of those complexes was shown to depend on their reduction potential. However suggestions exist that this result can be misleading for their in vivo activity, as platinum(IV) complexes are pro-drugs and might be inactive before reaching cancer cells. In a study of group of platinum(IV) complexes, derivatives of cisplatin and dichloroethylenediamineplatinum(II), a tendency for an increase of cytotoxic activity when lipophilicity increased was observed. However in a study of tetrakis(carboxylato)(1,2-diaminocyclohexane)platinum(IV) complexes, different cytotoxic activity of complexes possessing similar lipophilicity was observed. Hence lipophilicity of complex is important but it is not the only factor that determines complex activity. In other studies complexes of general structure cis, trans, cis-[PtNH3(RNH2)Cl2(OCOR')2] were examined. The research showed an increased activity of compounds with longer carbon chains of carboxylate axial ligands. It was also revealed that complexes with alicyclic amine ligands were more cytotoxic than those with aliphatic or aromatic amine ligands. Hall et al. revealed that platinum(IV) complexes, derivatives of cisplatin and dichloroethylenediamineplatinum(II), are active against DLD-1 colon cancer cell line in hypoxic environment. An examination of trans-dichlorodihydroxo(dimethylamine)(isopropylamine)platinum(IV) revealed its greater cytotoxic activity against A2780, CH1 and 41M human ovarian cancer cell lines, in vitro. Moreover this complex was shown to be active against A2780cisR, CH1cisR and 41McisR human ovarian cell lines which are resistant to cisplatin. Two platinum(IV) complexes: iproplatin (cis, trans, cis-dichlorodihydroxobis(isopropylamine)platinum(IV)) and tetraplatin (tetrachloro(cyclohexane-1,2-diamine)platinum(IV)) have had entered clinical trials. However iproplatin occurred to be less active than cisplatin and tetraplatin turned out to be neurotoxic. Presently two other complexes seem to be very promising: satraplatin (bis(acetato)amminedichlorocyclohexylamineplatinum(IV)) and adamplatin (bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV)). Both have entered clinical trials. There are some "nonstandard" approaches to investigating platinum complexes. For example platinum(IV) complexes with radioactive iodine isotope or with enzyme inhibitor were examined. Studies mentioned above present different approaches to searching for anticancer drugs among platinum(IV) complexes. Despite all encountered difficulties during researching platinum(IV) complexes, this group of compounds still seems to be potential source of new anticancer drugs.

10

HPLC-online TEAC - antioxidant activity of single compounds in complex mixtures

75%

Zietz M. , Schmidt S. , Rohn S. , Schreiner M. , Krumbein A. , Kroh L. W.

Polish Journal of Food and Nutrition Sciences

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2011

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tom 61

|

nr Suppl.1

11

Interactions of antitumor triazoloacridinones with DNA

75%

Koba M. , Konopa J.

Acta Biochimica Polonica

|

2007

|

tom 54

|

nr 2

297-306

EN

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.

12

Cyclic enkephalin-deltorphin hybrids containing a carbonyl bridge: structure and opioid activity

75%

Ciszewska M. , Ruszczyńska K. , Oleszczuk M. , Chung N. , Witkowska E. , Schiller P. , Wójcik J. , Izdebski J.

Acta Biochimica Polonica

|

2011

|

tom 58

|

nr 2

225-230

EN

Six hybrid N-ureidoethylamides of octapeptides in which an N-terminal cyclic structure related to enkephalin was elongated by a C-terminal fragment of deltorphin were synthesized on MBHA resin. The synthetic procedure involved deprotection of Boc groups with HCl/dioxane and cleavage of the peptide resin with 45 % TFA in DCM. d-Lys and d-Orn were incorporated in position 2, and Lys, Orn, Dab, or Dap in position 5. The side chains of the dibasic amino function were protected with the Fmoc group. This protection was removed by treatment with 55 % piperidine in DMF, and cyclization was achieved by treatment with bis-(4-nitrophenyl)carbonate. Using various combinations of dibasic amino acids, peptides containing a 17-, 18-, 19- or 20-membered ring structure were obtained. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse opioid activities were observed, depending on the size of the ring. Extension of the enkephalin sequence at the C-terminus by a deltorphin fragment resulted in a change of receptor selectivity in favor of the δ receptor. The conformational propensities of selected peptides were determined using the EDMC method in conjunction with data derived from NMR experiments carried out in water. This approach allowed proper examination of the dynamical behavior of these small peptides. The results were compared with those obtained earlier with corresponding N-(ureidoethyl)pentapeptide amides.

13

Structural studies of cysteine proteases and their inhibitors

75%

Grzonka Z. , Jankowska E. , Kasprzykowski F. , Kasprzykowska R. , Lankiewicz L. , Wiczk W. , Wieczerzak E. , Ciarkowski J. , Drabik P. , Janowski R. , Kozak M. , Jaskolski M. , Grubb A.

Acta Biochimica Polonica

|

2001

|

tom 48

|

nr 1

EN

Cysteine proteases (CPs) are responsible for many biochemical processes occurring in living organisms and they have been implicated in the development and progression of several diseases that involve abnormal protein turnover. The activity of CPs is regulated among others by their specific inhibitors: cystatins. The main aim of this review is to discuss the structure-activity relationships of cysteine proteases and cystatins, as well as of some synthetic inhibitors of cysteine proteases structurally based on the binding fragments of cystatins.

14

Interactions of antitumour triazoloacridinones with DNA

75%

Koba M. , Konopa J.

|

nr 2

EN

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.

15

Biological studies on pesticidal activity of aniline and [R]-2-phenoxypropionic acid derivatives

75%

Ziminska Z. , Krawczyk M. , Ptaszkowska J. , Ejmocki Z. , Ochal Z. , Gajadhur A. , Mizerski A.

Pestycydy

|

2001

|

nr 1-2

16

Structure-activity relationship study for fungicidal activity of 1-(4-phenoxymethyl-2-phenyl-[1,3]dioxolan-2-ylmethyl)-1H-1,2,4-triazole derivatives against rice blast

63%

Hoshi T. , Yamada K. , Yoshizawa Y. , Oh K.

Journal of Plant Protection Research

|

2015

|

tom 55

|

nr 4

EN

To explore new antifungal agents for rice blast control, the antifungal activity of a series of novel 1,2,4-triazole derivatives against Magnaporthe oryzae has been evaluated. The antifungal activity was determined by using in vitro mycelial growth inhibition tests. Among the 19 test compounds, we found that the compound 1-(4-phenoxymethyl-2-phenyl-[1,3]dioxolan-2-ylmethyl)-1H-1,2,4- triazole (Gj) displayed potent antifungal activity against M. oryzae. The IC50 value was found approximately 3.8±0.5 μM and the IC50 value of propiconazole was found to be approximately 3.7±0.2 μM, respectively. Structure-activity relationship studies on aromatic ring structures provided insight and information about the structural requirements for antifungal activity of this synthetic series against M. oryzae.

17

Studies on herbicidal efficacy of 5-difluoro- and trifluoromethylsulfonylbenzoimidazoles

63%

Krawczyk M. , Ziminska Z. , Zalecki S. , Ejmocki Z. , Legowiak Z. , Ochal Z. , Mizerski A.

Pestycydy

|

2001

|

nr 1-2

18

Leki przeciw grypie. Synteza tamiflu® - leku gromadzonego, aby zapobiec epidemii ptasiej grypy

51%

Karchier M. , Michalak K. , Wicha J.

Wiadomości Chemiczne

|

2007

|

tom [Z] 61, 1-2

7-42

EN

Influenza (flu) and related viral infections present a constant threat to public health. World-wide efforts have been recently initiated (coordinated by WHO) to prevent global epidemic in view of spreading deadly bird flu virus (H5N1) among people. Attention has been focused on Tamiflu® (1, Figure 1), synthetic, orally active drug manufactured by Hoffmann - La Roche On the surface of the flu virus there are located two proteins important for infecting animal cell: hemagglutinin and neuraminidase (sialidase). Hemagglutinin is responsible for the recognition of specific sialic acids in the cell membrane glycoconjugates; neuraminidase is involved in subsequent hydrolysis of sialic acid residue and is crucial for the virus propagation. Sialic acids are sugar-related keto-acids, as neuraminic acid 2. Their structure is specific for a given species. Functions of hemagglutinin or neuraminidase have been targeted in systematic search for anti-flu drugs. The first efficient neuraminidase competitive inhibitor Relanza® (Zanamivir) has been obtained as a mimic of hypothetic oxonium ion involved in sialic acid hydrolysis. Many structures related to Zanamivir have been investigated]. The most successful line of research has been aimed at synthesis of carbocyclic neuraminic acid derivatives from (-)-quinic or (-)-shikimic acids. The Gilead-Roche "first generation" analogue with the double bond oriented toward the hydroxy-group 33 proved more active than its counterpart 34. Further modification of the structure 33 was based on X-ray analysis of protein - inhibitor complexes and led to Tamiflu®. Prime synthesis of Tamiflu® from (-)-shikimic acid involved several steps. Since this starting material is rather expensive more economic approaches have been studied. The technological approach to the key epoxide 75 from (-)-quinic acid involves bicyclic lactone 70 controlled dehydration to form 73 and regiospecific acetal reduction using borane-dimethylsulfide complex in the presence of a silylating agent. Use of the developed methods and shikimic acid as the starting material allowed for an efficient access to the target epoxide 75. The epoxide 75 has been transformed into the final product in several steps. Most advanced synthetic routes transforming 75 into Tamiflu® rely upon the use of tert-butylamine and then diallylamine. Current studies on transformation of glucose into shikimic acid by genetically modified strain of Escherichia coli are likely to secure supplies of this convenient starting material for Tamiflu® production. E. J. Corey et al. have developed enantioselective total synthesis of Tamiflu®. [2+4] cycloaddition reaction of butadiene and trifluoroethylacrylate in the presence of a chiral oxazoborolidine catalyst provided cyclohex-3-enecarboxylic acid derivative (87, Scheme 19). Transformation of 87 into 99 embraced several steps, including the novel haloamidation (86 into 97). The synthesis route involved 12 steps and afforded Tamiflu® in 25% overall yield. Catalytic enantioselective reaction of the easily accessible meso-aziridine 101with trimethylsilylazide provided the cornerstone to total synthesis of Tamiflu® by M. Shibasaki et al. [48]. The synthetic route from azide 102 to the target involved several steps (Schemes 23 and 24). Among them the efficient allylic oxidation of 109 and the nickel-catalyzed conjugate addition of trimethylsilylcyanide to ?,?-unsaturated ketone 110 that contribute to general synthetic methodology. In the synthesis developed by Cong i Yao [51], the starting material - serine-derived aldehyde 117 (Garner's aldehyde, Scheme 25) has been selected from the "chiral pool". The synthesis involves a sequence of diastereoselective reactions and the ring-closure metathesis reaction (130 into 131) using the II generation Grubbs catalyst. Approaches to Tamiflu® illustrate the impressive achievements of organic synthesis. However, at present the high cost of this drug may hamper its broader application.

19

Synthesis and biological effects of insect oostatic peptide Neb-colloostatin

51%

Kuczer M. , Skonieczna M. , Wasielewski O. , Rosinski G. , Konopinska D.

Pestycydy

|

2005

|

nr 3

39-47

20

New biological activity of NPF-related peptides in insects

51%

Skonieczna M. , Grodecki S. , Konopinska D. , Rosinski G.

Pestycydy

|

2005

|

nr 4

91-98