8-Halo-substituted naphtho[2,3-b]thiophene-4,9-diones as redox-active inhibitors of keratinocyte hyperproliferation with reduced membrane-damaging properties.

A series of 8-chloronaphtho[2,3-b]thiophene-4,9-diones and also some 8-bromo analogues were prepared. The compounds were evaluated for their potencies to suppress keratinocyte hyperproliferation using the human keratinocyte line HaCaT as the primary test system. Structure-activity relationship studies revealed that replacement of the phenolic group of an earlier series with an 8-halogen atom retained the inhibitory potency against keratinocyte hyperproliferation with IC50 values in the submicromolar range.

Synthesis and structure-activity relationships of lapacho analogues. 2. Modification of the basic naphtho[2,3-b]furan-4,9-dione, redox activation, and suppression of human keratinocyte hyperproliferation by 8-hydroxynaphtho[2,3-b]thiophene-4,9-diones.

The basic structure of linearly anellated lapacho quinones, naphtho[2,3-b]furan-4,9-dione (7), was modified in the search for novel agents against keratinocyte hyperproliferation. The synthesis and structure-activity relationships of several heterocycle-fused naphthoquinones as well as a full range of 2- and 7-substituted derivatives of one of these, 8-hydroxynaphtho[2,3-b]thiophene-4,9-dione (8a), are described. Out of a total of 71 analogues, particularly 2-thenoyl-substituted 26l, 2-nicotinoyl-substituted 26m, and 2-oxadiazole-substituted 35a compared favorably with the antipsoriatic agent anthralin.