Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

International audienceHuman tyrosinase (hsTYR) catalyzes the key steps of melanogenesis, making it a privileged target for reducing melanin production in vivo. However, very few hsTYR inhibitors have been reported so far in the literature, whereas thousands of mushroom tyrosinase (abTYR) inhibitors are known. Yet, as these enzymes are actually very different, including at their active sites, there is an urgent need for new true hsTYR inhibitors in order to enable human-directed pharmacological and dermocosmetic applications without encountering the inefficiency and toxicity issues currently triggered by kojic acid or hydroquinone. Starting from the two most active compounds reported to date, i.e. a 2-hydroxypyridine-embedded aurone and thiamidol, we combined herein key structural elements and developed new nanomolar hsTYR inhibitors with cell-based activity. From a complete series of thirty-eight synthesized derivatives, excellent inhibition values were obtained for two compounds in both human melanoma cell lysates and purified hsTYR assays, and a promising improvement was observed in whole cell experiments

Resorcinol-based hemiindigoid derivatives as human tyrosinase inhibitors and melanogenesis suppressors in human melanoma cells

Human tyrosinase (hsTYR) catalyzes the key steps of melanogenesis, making it a privileged target for reducing melanin production in vivo. However, very few hsTYR inhibitors have been reported so far in the literature, whereas thousands of mushroom tyrosinase (abTYR) inhibitors are known. Yet, as these enzymes are actually very different, including at their active sites, there is an urgent need for new true hsTYR inhibitors in order to enable human-directed pharmacological and dermocosmetic applications without encountering the inefficiency and toxicity issues currently triggered by kojic acid or hydroquinone. Starting from the two most active compounds reported to date, i.e. a 2-hydroxypyridine-embedded aurone and thiamidol, we combined herein key structural elements and developed new nanomolar hsTYR inhibitors with cell-based activity. From a complete series of thirty-eight synthesized derivatives, excellent inhibition values were obtained for two compounds in both human melanoma cell lysates and purified hsTYR assays, and a promising improvement was observed in whole cell experiments

Digital Interventions for Mental Disorders:Key Features, Efficacy, and Potential for Artificial Intelligence Applications

Mental disorders are highly prevalent and often remain untreated. Many limitations of conventional face-to-face psychological interventions could potentially be overcome through Internet-based and mobile-based interventions (IMIs). This chapter introduces core features of IMIs, describes areas of application, presents evidence on the efficacy of IMIs as well as potential effect mechanisms, and delineates how Artificial Intelligence combined with IMIs may improve current practices in the prevention and treatment of mental disorders in adults. Meta-analyses of randomized controlled trials clearly show that therapist-guided IMIs can be highly effective for a broad range of mental health problems. Whether the effects of unguided IMIs are also clinically relevant, particularly under routine care conditions, is less clear. First studies on IMIs for the prevention of mental disorders have shown promising results. Despite limitations and challenges, IMIs are increasingly implemented into routine care worldwide. IMIs are also well suited for applications of Artificial Intelligence and Machine Learning, which provides ample opportunities to improve the identification and treatment of mental disorders. Together with methodological innovations, these approaches may also deepen our understanding of how psychological interventions work, and why. Ethical and professional restraints as well as potential contraindications of IMIs, however, should also be considered. In sum, IMIs have a high potential for improving the prevention and treatment of mental health disorders across various indications, settings, and populations. Therefore, implementing IMIs into routine care as both adjunct and alternative to face-to-face treatment is highly desirable. Technological advancements may further enhance the variability and flexibility of IMIs, and thus even further increase their impact in people’s lives in the future