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Structure‐function relationship of new anthralin derivatives assayed for growth inhibition and cytotoxicity in human keratinocyte cultures
Author(s) -
Bonnekoh Bernd,
Tanzer Helene,
Seidel Matthias,
Geisel Jürgen,
Merk Hans F.,
Mahrle Gustav,
Wiegrebe Wolfgang
Publication year - 1991
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.2503241115
Subject(s) - cytotoxicity , keratinocyte , chemistry , function (biology) , stereochemistry , cell culture , structure–activity relationship , biological activity , biochemistry , in vitro , microbiology and biotechnology , biology , genetics
HaCaT keratinocyte cultures were exposed to twelve hydrophilic anthralin derivatives 1 to 12 with substituents at C‐1 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 μM treatment growth was determined by cellular protein content, 3 H‐thymidine‐and 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 1‐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.