Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    New triazine derivatives as potent modulators of multidrug resistance (1992)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 35 (1992), S. 2481-2496 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00091a017
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Synthesis and Evaluation of 9-Hydroxy-5-methyl- (and 5,6-dimethyl)-6H-pyrido[4,3-b]carbazole-1-N-[(dialkylamino)alkyl]carboxamides, a New Promising Series of Antitumor Olivacine Derivatives (1994)
    s.l. : American Chemical Society
    Journal of medicinal chemistry 37 (1994), S. 2445-2452 
    Details
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/jm00041a024
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Relationship between the cellular accumulation and the cytotoxicity of S12363, a new vinca alkaloid derivative (1992)
    Springer
    Cancer chemotherapy and pharmacology 29 (1992), S. 367-374 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary S 12363, a new vinca alkaloid derivative, was considerably more cytotoxic to murine L1210 cells and five human tumor cell lines (HL60, HT-29, COLO 320DM, NCI-H460, and PANC-1) than was vincristine (VCR) or vinblastine (VLB). S 12363 bound to tubulin in crude extracts from brain or L1210 cells with an affinity similar to that of VLB and VCR (apparentK d value: 1.1–1.6, 1.2–1.7, and 0.6–0.8 μM, respectively). After 1 h exposure, the accumulation of 20 nM [3H]-S 12363 by L1210 cells was 4-to 18-fold that of [3H]-VLB and [3H]-VCR, respectively. After the cells had been preloaded for 1 h with the labeled drugs and then incubated for 3 h in drug-free medium, 37%–55% of the [3H]-S 12363 was retained by the cells vs 36%–47% of the [3H]-VCR and 〈6% of the [3H]-VLB. Similar results were obtained for the five human cell lines tested. The accumulation factors (intracellular vs extracellular concentrations) found for [3H]-S 12363 (54- to 167-fold) were significantly higher than those observed for [3H]-VCR (5- to 14-fold) or [3H]-VLB (19- to 41-fold). 〉90% of the radioactivity extracted from L1210 cells that had been treated with [3H]-S 12363 was recovered as unmodified drug, demonstrating that [3H]-S 12363 was not metabolized by these cells. S 12362, which differs from S 12363 only in the absolute configuration of the asymmetric carbon atom of its α-aminophosphonic side chain, was 300 times less cytotoxie, bound to tubulin with a lower affinity (apparentK d value, 4.9–9.6 μm), and was neither accumulated nor retained by the cells. Taken together, these results demonstrate that the potency of S 12363 is due at least in part to its cellular accumulation and retention.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686005
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    In vitro cytotoxicity of S16020-2, a new olivacine derivative (1996)
    Springer
    Investigational new drugs 14 (1996), S. 169-180 
    Details
    ISSN: 1573-0646
    Keywords: S16020-2 ; adriamycin ; multidrug resistance ; P-glycoprotein ; flow cytometry ; topoisomerases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary S16020-2 is a new olivacine derivative which has recently shown a marked antitumor activity in various experimental models. This study was undertaken in order to measure the inhibition of the proliferation of various sensitive and resistant tumor cell lines, by S16020-2, and to obtain information concerning its mechanism of action. For a continuous exposure, S16020-2 was as cytotoxic as adriamycin (ADR) (mean IC50 of about 28 nM) and on average, 46 fold more potent than elliptinium acetate (ELP), against a panel of 20 non-multidrug resistant cell lines. With a short exposure (1 hour) followed by a post-incubation of 95 hours in drug-free medium, S16020-2 was 5 and 6 fold more cytotoxic than ADR for human lung A549 and murine melanoma B16 cells, respectively. Furthermore, S16020-2 inhibited more actively the formation of colonies issued from proliferating cells, compared to colonies issued from quiescent A549 cells. Because quiescent cells demonstrated a 3 fold lower level of topoisomerase IIα (topo II) than proliferating cells, these results suggest that this enzyme could be a potential target for S16020-2. In addition, as demonstrated by flow cytometric studies, S16020-2 intercalated into DNA and induced a cell cycle arrest in G2. Cell lines displaying the multidrug resistance (MDR) phenotype, P388/ADR-1, P388/ADR, P388/VCR-20, KB-A1, DC-3F/AD, S1/tMDR, and Colo320DM, were more sensitive to S16020-2 than to ADR or ELP, as shown by the mean resistance factors, 8, 201, and 23 respectively. In addition, the two cell lines displaying the pure classical MDR phenotype, linked exclusively to the P-glycoprotein (P-gp) overexpression (P388/VCR-20 and S1/tMDR), were as sensitive to S16020-2 as their sensitive parental counterparts, although they were resistant to ADR. S16020-2 is thus one of the most potent olivacine and ellipticine derivative yet characterized. The good cytotoxicity of S16020-2 against cells displaying a P-gp-mediated multidrug resistance, and its antitumor activity in vivo delineate an important chemotherapeutic potential for this drug.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00210788
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    In vitro andin vivo circumvention of multidrug resistance by Servier 9788, a novel triazinoaminopiperidine derivative (1992)
    Springer
    Investigational new drugs 10 (1992), S. 137-148 
    Details
    ISSN: 1573-0646
    Keywords: drug resistance ; S 9788 ; vinca-alkaloids ; anthracyclines ; epipodophyllotoxins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary S 9788 is a novel triazinoaminopiperidine derivative which does not belong to any of the classes of compounds known to reverse multidrug resistance (MDR). S 9788 was far more potent than verapamil (VRP) in reversing resistance to adriamycin (ADR) in the ADR-selected murine leukaemia cell lines P388/ADR-1 and P388/ADR-10, and the human chronic myelogenous leukaemia K562/R. Fold reversion with S 9788 (5μM was, respectively, 3.5, 5.4 and 11.3 times greater than that with VRP (5μM). S 9788 was also a more potent reversant of ADR resistance in the intrinsically resistant human colon adenocarcinoma COLO 320DM (2.3 fold), and of vincristine (VCR) resistance in the human MDR1 gene-transfected squamous lung carcinoma line S1/tMDR1 (5.6 fold). The activity of S 9788 depended on both the MDR cell line and the cytotoxic agent. S 9788 (50–100 mg/kg/d) administered IP once a day on days 1–4 resulted in a dose-dependent increase in the chemotherapeutic effect of VCR (0.25 mg/kg/d) in P388/VCR-bearing mice and ADR (4 mg/kg/d) in P388/ADR-bearing mice. Increases in antitumor activity were (% T/C) of +20–34% in the P388/ADR model and +50–78% in the P388/VCR model with respect to cytotoxic agent treatment alone. S 9788 appeared to be devoid of toxicity at its effective doses. The mechanism of action of S 9788 is unknown but S 9788 (0.5–10μM) induced a dose-dependent increase in ADR accumulation in KB-Al cells and compared to verapamil its effect was twice as active and approximately seven times more potent. We conclude that S 9788 is a novel agent capable of reversing MDRin vitro andin vivo, and whose pharmacological profile warrants its selection as a candidate drug for eventual assessment in the clinic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00877238
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...