P23 SUBSTITUTED INDOLE CARBOXYLIC ACIDS ARE POTENT AND SELECTIVE INHIBITORS OF EITHER TYPE-1 OR TYPE-2 HUMAN STEROID 5a-REDUCTASE

¹C.Gerst, ²M.Dalko, ²P.Pichaud, ²J.B.Galey, ¹B.Buan and ¹B.A.Bernard; ¹L’Oréal Recherche Avancée, Hair Biology Group, Centre de Recherche C.Zviak, 90 rue du Général Roguet, 92110 Clichy, France, ²L’Oréal Recherche Avancée, Department of Chemistry, 1 avenue E.Schueller, Aulnay sous Bois, France

Steroid 5a-reductase catalyzes the reduction of Testosterone into the very potent androgen Dihydrotestosterone. The different tissue expression patterns of the two isoforms of 5a -reductase, 5a-R1 and 5a-R2, has prompted studies directed towards the synthesis of selective type 1 or type 2 5a-reductase inhibitors. In this present work, we have performed a structure/activity study on the inhibitory potential of indole carboxylic acids against hair follicle 5a-reductase activity. We have demonstrated that this class of molecules were potent inhibitors of either 5a-R1 or 5a-R2 or both depending on i) substituents in positions 4, 5 or 6 and ii) the presence of a free carboxylic group. We have also found that only 5a-R1 or 5a-R1/R2 inhibitors were able to inhibit 5a-reductase activity in plucked hairs from female volunteers or in freshly isolated female hair follicles, selective 5a-R2 inhibitors being inactive.