ANTHRALIN - HOW DOES IT ACT AND AVE THERE MORE FAVORABLE DERIVATIVES

Anthralin is still the most effective and safest therapeutic agent for treatment of psoriasis. Our data mag assist toward an understanding o f its mode of action and introduce new derivatives, more antiprolifera tive and less toxic than anthralin in vitro. Anthralin exerts a direct effect on keratinocytes and leukocytes. In time-lapse studies it sign ificantly prolonged the prophase of mitotic keratinocytes in subtoxic doses and suppressed the expression of keratin 6 mRNA in the immediate ly suprabasal layer of psoriatic epidermis in vivo. Anthralin inhibits the transformation of lymphocytes and the release of reactive oxygen species from activated leukocytes, in vitro. We provide evidence that these effects of anthralin are mediated by protein kinase C. Twelve ne w hydrophilic derivatives of anthralin, including a 1,8-dimethosy comp ound, as well as C-2 and C-10 substituted anthrones were tested on hum an keratinocytes. The antiproliferative effect of those derivatives be aring lacton rings at a C-10, consisting of 4, 5, or 6 C atoms, exceed ed that of anthralin and were equally or less cytotoxic than the paren t drug. These compounds had no pro-drug character in vitro, since they did not metabolize via anthralin, as shown by HPLC. These data indica te that there may be anthralin derivatives with more favourable proper ties for topical therapy than anthralin itself.