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Novel 11beta-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV
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Novel 11beta-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV
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Novel 11beta-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV
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Journal Article
Novel 11beta-hydroxysteroid dehydrogenase 1 inhibitors reduce cortisol levels in keratinocytes and improve dermal collagen content in human ex vivo skin after exposure to cortisone and UV
2017
Overview
Activity and selectivity assessment of new bi-aryl amide 11[beta]-hydroxysteroid dehydrogenase 1 (11[beta]-HSD1) inhibitors, prepared in a modular manner via Suzuki cross-coupling, are described. Several compounds inhibiting 11[beta]-HSD1 at nanomolar concentrations were identified. Compounds 2b, 3e, 7b and 12e were shown to selectively inhibit 11[beta]-HSD1 over 11[beta]-HSD2, 17[beta]-HSD1 and 17[beta]-HSD2. These inhibitors also potently inhibited 11[beta]-HSD1 activity in intact HEK-293 cells expressing the recombinant enzyme and in intact primary human keratinocytes expressing endogenous 11[beta]-HSD1. Moreover, compounds 2b, 3e and 12e were tested for their activity in human skin biopsies. They were able to prevent, at least in part, both the cortisone- and the UV-mediated decreases in collagen content. Thus, inhibition of 11[beta]-HSD1 by these compounds can be further investigated to delay or prevent UV-mediated skin damage and skin aging.
Publisher
Public Library of Science
Subject
