Potential antipsoriatic agents: Lapacho compounds as potent inhibitors of HaCaT cell growth

Citation
K. Muller et al., Potential antipsoriatic agents: Lapacho compounds as potent inhibitors of HaCaT cell growth, J NAT PROD, 62(8), 1999, pp. 1134-1136
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Agricultural Chemistry","Pharmacology & Toxicology
Journal title
JOURNAL OF NATURAL PRODUCTS
ISSN journal
0163-3864 → ACNP
Volume
62
Issue
8
Year of publication
1999
Pages
1134 - 1136
Database
ISI
SICI code
0163-3864(199908)62:8<1134:PAALCA>2.0.ZU;2-D
Abstract
A number of lapacho compounds, representing the most common constituents of the inner bark of Tabebuia impetiginosa, together with some synthetic anal ogues, were evaluated in vitro against the growth of the human keratinocyte cell line HaCaT. With an IC50 value of 0.7 mu M, beta-lapachone (4) displa yed activity comparable to that of the antipsoriatic drug anthralin. 2-Acet yl-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 grow th with an IC50 value of 0.35 mu M Furthermore, other active constituents o f lapacho inhibited keratinocyte growth, with IC50 values in the range of 0 .5-3.0 mu M. However, as already observed with anthralin, treatment of HaCa T cells with these potent lapacho compounds also caused remarkable damage t o the plasma membrane. This was documented by leakage of lactate dehydrogen ase into the culture medium, which significantly exceeded that of the vehic le control. Because of their potent activity against the growth of human ke ratinocytes, some lapacho-derived compounds appear to be promising as effec tive antipsoriatic agents.