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As part of continued efforts for the development of new tyrosinase inhibitors, (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one derivatives (1a - 1l) were rationally synthesized and evaluated for their inhibitory potential in vitro. These compounds were designed and synthesized based on the structural attributes of a β-phenyl-α,β-unsaturated carbonyl scaffold template. Among these compounds, (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-iminothiazolidin-4-one (1e, MHY773) exhibited the greatest tyrosinase inhibition (IC = 2.87 μM and 8.06 μM for monophenolase and diphenolase), and outperformed the positive control, kojic acid (IC = 15.59 and 31.61 μM). The kinetic and docking studies demonstrated that MHY773 interacted with active site of tyrosinase. Moreover, a melanin quantification assay demonstrated that MHY773 attenuates α-melanocyte-stimulating hormone (α-MSH) and 3-isobutyl-1-methylxanthine (IBMX)-induced melanin contents in B16F10 melanoma cells. Taken together, these data suggest that MHY773 suppressed the melanin production via the inhibition of tyrosinase activity. MHY773 is a promising for the development of effective pharmacological and cosmetic agents for skin-whitening.

The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720. We performed an in vitro SIRT1 activity assay to identify the strongest SIRT1 activator. The assay confirmed MHY2233 to be the strongest SIRT1 activator (1.5-fold more potent than resveratrol), and docking simulation showed that the binding affinity of MHY2233 was higher than that of resveratrol and SRT1720. To investigate its beneficial effects, db/db mice were orally administered MHY2233 for 1 month, and various metabolic parameters were assessed in the serum and liver tissues. MHY2233 markedly ameliorated insulin signaling without affecting body weight in db/db mice. In particular, the mRNA expression of lipogenic genes, such as acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein, which increased in db/db mice, decreased following oral treatment with MHY2233. In conclusion, the novel SIRT1 activator MHY2233 reduced lipid accumulation and improved insulin resistance. This finding may contribute toward therapeutic approaches for fatty liver disease and glucose tolerance.

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Prostate cancer is the most common type of cancer diagnosed in men. In 2018, prostate cancer represented 19% of all cancer diagnoses in men in the United States, which is the highest in the entire world (Siegel et al., 2018). The current front-line therapies for prostate cancer are either surgical removal of the tumor or radiation therapy, regardless of androgen sensitivity (Balk and Knudsen, 2008; Schröder et al., 2012). The androgen receptor (AR) is a transcription factor that plays a pivotal role in the regulation of androgen levels in tumors, and in the development of advanced prostate cancer (Balk, 2009). However, the mechanisms underlying the initiation and progression of prostate cancer are still not fully understood. In the early stages of prostate cancer, patients usually receive anti-androgen therapy; however, relapses occur frequently within 1 to 3 years, and patients then require treatment with a continuous conventional therapy. The effectiveness of chemotherapy remains limited, and is associated with serious adverse effects and a compromised quality of life (Keizman and Eisenberger, 2010; Kuban et al., 2013). Owing to increased mortality rates and failure of conventional chemotherapy in advanced prostate cancer patients, there is an urgent need for new alternative therapies (Bilusic et al., 2017;

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