Incorporation of 3H-thymidine into DNA: Inhibition by dithranol and its di- and triacetate

Plumier, E.; Wappes, B.; Wiegrebe, Wolfgang

doi:10.1007/bf00413363

Cited by 6 publications

(2 citation statements)

References 11 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are in good agreement with the findings for a very similar compound, namely 1,8,9-trimethoxy-anthracene, which proved to be ineffective against psoriatic lesions 39 *. However, contrary to the "minimum structure" concept, an animal study by Phonier et al 40) on 1,8,9-triacetoxy-anthracene revealed that the antiproliferative activity of this derivative, even though less than that of anthralin, did not depend on degradation to a "minimum structure" compound. Thus, the study denied the pro-drug character of 1,8,9-triacetoxy-anthracene which had initially been suggested 36 ' 37 ' 41 *.…”

Section: Significance Of Free Hydroxy Group At C-lmentioning

confidence: 83%

“…Thus, the study denied the pro-drug character of 1,8,9-triacetoxy-anthracene which had initially been suggested 36 ' 37 ' 41 *. Also not in favor of the "minimum structure" concept was the finding that the topically applied antiproliferatively active 1,8-diacetoxy-anthracene was not converted to a compound with a free C-l hydroxy group 40) . In contrast to the results with the HaCaT keratinocytes we recently found nonphenolic anthrones to be more active as inhibitors of arachidonic acid lipoxygenase from bovine polymorphonuclear leucocytes than anthralin, suggesting a different mode of action 42) .…”

Section: Significance Of Free Hydroxy Group At C-lmentioning

confidence: 99%

See 1 more Smart Citation

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Bonnekoh

Tanzer

Seidel

et al. 1991

Archiv der Pharmazie

View full text Add to dashboard Cite

HaCaT keratinocyte cultures were exposed to twelve hydrophilic anthralin derivatives 1 to 12 with substituents at C-l and C-8 of the anthrone skeleton, of one H at C-10 and of both H's at C-10 by lacton rings ( fig. 1). After 3 uM treatment growth was determined by cellular protein content, ^-thymidineand 14 C-amino-acid-uptake and cytotoxicity by the release of cytoplasmic LDH into the culture medium.-In comparison to acetone control (100%) anthralin suppressed mean protein content, as well as DNA-and protein-synthesis to 33, 28, and 21%, respectively, and the drug revealed an enzyme release of 660%. In relation to the parent drug we found similar cell growth inhibitory effects of compounds 4, 6, 8, 9, 10, and 12. Deriv. 4, 8, and 10 were, however, to some extent less cytotoxic than anthralin, whereas deriv. 6, 9, and 12 were in the same range. An extreme suppression of growth parameters which differed from the anthralin effect by a factor 0.5-0.8 was caused by deriv. 11, showing the same cytotoxicity. Deriv. 1, 2, 3,5, and 7 did not demonstrate any cytotoxicity. Concerning growth parameters, deriv. 2 induced a slight stimulation, deriv. 3 and 7 were completely ineffective, deriv. 1 and 5 induced slightly to moderately inhibited proliferation but both being much less effective than anthralin. These data indicate that the "minimum structure" concept by Krebs and Schaltegger -claiming l-hydroxy-9-anthrone as a precondition for clinical antipsoriatic potency -is not valid at least in cell-biological tests and point toward possible usefulness of some experimental model compounds as alternative antipsoriatics.

show abstract

Section: Significance Of Free Hydroxy Group At C-lmentioning

confidence: 83%

Section: Significance Of Free Hydroxy Group At C-lmentioning

confidence: 99%

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Bonnekoh

Tanzer

Seidel

et al. 1991

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

Dithranol, Vitamin D3-Analoga und 8-Methoxypsoralen

Gloor¹

2000

Dermatologische Externatherapie

View full text Add to dashboard Cite

Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro

1991

View full text Add to dashboard Cite

The hyperproliferative human keratinocyte line (HaCaT) was tested for dithranol tolerance (tachyphylaxis) at the cellular level. At day 4 after seeding, keratinocytes were treated with 0.3 or 1.0 microM dithranol. Data were compared with those from experiments including additional pretreatments with 0.3 microM at day 3, or at days 1 and 3. Protein content, DNA synthesis and protein synthesis (incorporation of 3H-thymidine and 14C-amino acids per protein) were determined at 24, 48 and 72 h after the last drug exposure. Protein content of attached cells decreased in relation to dose and frequency of treatments. Inhibition of DNA and protein synthesis (38.2% and 32.3%, respectively) also occurred 24 h after a single treatment with 0.3 microM dithranol, but was only 18.4% and 9.1% after pretreatment twice with 0.3 microM dithranol. This tolerance reaction in vitro, after repeated dithranol exposure of human keratinocytes, may be explained by a selective loss of drug-sensitive cells.

show abstract

Incorporation of 3H-thymidine into DNA: Inhibition by dithranol and its di- and triacetate

Cited by 6 publications

References 11 publications

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures

Dithranol, Vitamin D3-Analoga und 8-Methoxypsoralen

Repeated treatment with dithranol induces a tolerance reaction in keratinocytes in vitro

Contact Info

Product

Resources

About