title: Potential antipsoriatic agents: lapacho compounds as potent inhibitors of HaCaT cell growth.
abstract: A number of lapacho compounds, representing the most common constituents of the inner bark of Tabebuia impetiginosa, together with some synthetic analogues, were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. With an IC(50) value of 0.7 microM, beta-lapachone (4) displayed activity comparable to that of the antipsoriatic drug anthralin. 2-Acetyl-8-hydroxynaphtho[2,3-b]furan-4,9-dione (7), which was prepared in a four-step synthesis from 2,8-dihydroxy-1, 4-naphthoquinone, was the most potent inhibitor among the known lapacho-derived compounds and inhibited cell growth with an IC(50) value of 0.35 microM. Furthermore, other active constituents of lapacho inhibited keratinocyte growth, with IC(50) values in the range of 0.5-3.0 microM. However, as already observed with anthralin, treatment of HaCaT cells with these potent lapacho compounds also caused remarkable damage to the plasma membrane. This was documented by leakage of lactate dehydrogenase into the culture medium, which significantly exceeded that of the vehicle control. Because of their potent activity against the growth of human keratinocytes, some lapacho-derived compounds appear to be promising as effective antipsoriatic agents.
authors.affiliation: Institut für Pharmazeutische Chemie, Westfälische Wilhelms-Universität Münster, Hittorfstrasse 58-62, D-48149 Münster, Germany. kmuller@uni-muenster.de
authors.forename: K
authors.initials: K
authors.lastname: Müller
authors.forename: A
authors.initials: A
authors.lastname: Sellmer
authors.forename: W
authors.initials: W
authors.lastname: Wiegrebe
mesh_terms: D000287:Administration, Topical; D000875:Anthralin / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002455:Cell Division; D002460:Cell Line; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology; D007641:Keratolytic Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D011565:Psoriasis / Q000188:drug therapy*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000893:Anti-Inflammatory Agents; D007641:Keratolytic Agents; D009285:Naphthoquinones; C029244:xyloidone; C014638:beta-lapachone; C008252:lapachol; D007770:L-Lactate Dehydrogenase; D000875:Anthralin