SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "LAR1:uu ;pers:(Larsson Rolf);pers:(Felth Jenny);pers:(Bohlin Lars);lar1:(uu)"

Sökning: LAR1:uu > Larsson Rolf > Felth Jenny > Bohlin Lars > Uppsala universitet

  • Resultat 1-4 av 4
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Felth, Jenny, 1979-, et al. (författare)
  • Gambogic acid is cytotoxic to cancer cells through inhibition of the ubiquitin-proteasome system
  • 2013
  • Ingår i: Investigational new drugs. - 0167-6997. ; 31:3, s. 587-598
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Gambogic acid (GA), displays cytotoxicity towards a wide variety of tumor cells and has been shown to affect many important cell-signaling pathways. In the present work, we investigated the mechanism of action of GA by analysis of drug-induced changes in gene expression profiles and identified GA and the derivative dihydro GA as possible inhibitors of the ubiquitin-proteasome system (UPS). Both GA and dihydro GA inhibited proteasome function in cells resulting in the accumulation of polyubiquitin complexes. In vitro experiments showed that both GA and dihydro GA inhibited 20S chymotrypsin activity and the inhibitory effects of GA and dihydro GA on proteasome function corresponded with apoptosis induction and cell death. In conclusion, our results show that GA and dihydro GA exert their cytotoxic activity through inhibition of the UPS, specifically by acting as inhibitors of the chymotrypsin activity of the 20S proteasome.
  •  
2.
  • Hallböök, Helene, et al. (författare)
  • Ex Vivo Activity of Cardiac Glycosides in Acute Leukaemia
  • 2011
  • Ingår i: PLoS ONE. - 1932-6203. ; 6:1, s. e15718
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:Despite years of interest in the anti-cancerous effects of cardiac glycosides (CGs), and numerous studies in vitro and in animals, it has not yet been possible to utilize this potential clinically. Reports have demonstrated promising in vitro effects on different targets as well as a possible therapeutic index/selectivity in vitro and in experimental animals. Recently, however, general inhibition of protein synthesis was suggested as the main mechanism of the anti-cancerous effects of CGs. In addition, evidence of species differences of a magnitude sufficient to explain the results of many studies called for reconsideration of earlier results.Principal Findings:In this report we identified primary B-precursor and T-ALL cells as being particularly susceptible to the cytotoxic effects of CGs. Digitoxin appeared most potent and IC50 values for several patient samples were at concentrations that may be achieved in the clinic. Significant protein synthesis inhibition at concentrations corresponding to IC50 was demonstrated in colorectal tumour cell lines moderately resistant to the cytotoxic effects of digoxin and digitoxin, but not in highly sensitive leukaemia cell lines.Conclusion:It is suggested that further investigation regarding CGs may be focused on diagnoses like T-and B-precursor ALL.
  •  
3.
  • Roggen, Heidi, et al. (författare)
  • 2-Substituted agelasine analogs : Synthesis and biological activity, and structure and reactivity of synthetic intermediates
  • 2011
  • Ingår i: Pure and Applied Chemistry. - 0033-4545. ; 83:3, s. 645-653
  • Tidskriftsartikel (refereegranskat)abstract
    • 2-Substituted N-methoxy-9-methyl-9H-purin-6-amines were synthesized either from their corresponding 6-chloro-9-methyl-9H-purines or 2-chloro-N-methoxy-9-methyl-9H-purin-6-amine. Great diversity in the amino/imino tautomeric ratios was observed and calculated based on H-1 NMR. The tautomers were identified by 1D and 2D H-1, C-13, and N-15 NMR techniques, and showed significant variation both in C-13 and N-15 shift values. Comparison of the tautomeric ratios with Hammett F values revealed that as the field/inductive withdrawing abilities of the 2-substituent increased, the ratio of amino: imino tautomers was shifted toward the amino tautomer. Computational chemistry exposed the significance of hydrogen bonding between solvent and the compound in question to reach accurate predictions for tautomeric ratios. B3LYP/def2-TZVP density functional theory (DFT) calculations resulted in quantitatively more accurate predictions than when employing the less expensive BP86 functional. N-7-Alkylation of the 2-substituted N-methoxy-9-methyl-9H-purin-6-amines showed that when the field/inductive withdrawing ability of the 2-substituent reached a certain point the reactivity drastically dropped. This correlated with the atomic charges on N-7 calculated using a natural bond orbital (NBO) analysis. Biological screening of the final 2-substituted agelasine analogs indicated that the introduction of a methyl group in the 2-position is advantageous for antimycobacterial and antiprotozoal activity, and that an amino function may improve activity against several cancer cell lines.
  •  
4.
  • Roggen, Heidi, et al. (författare)
  • Antimicrobial and antineoplastic activities of Agelasine analogs modified in the purine 2-position
  • 2011
  • Ingår i: Archiv der Pharmazie. - 0365-6233. ; 344:1, s. 50-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Agelasines are 7,9-dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2-position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U-937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC-5 cells. The results indicate that the introduction of a methyl group in the purine 2-position is beneficial for antimycobacterial and antiprotozoal activity, and that amino groups may enhance activity against several cancer cell lines.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-4 av 4
 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy