Lumazine peptides from the marine-derived fungus Aspergillus terreus.

Terrelumamides A (1) and B (2), two new lumazine-containing peptides, were isolated from the culture broth of the marine-derived fungus Aspergillus terreus. From the results of combined spectroscopic and chemical analyses, the structures of these compounds were determined to be linear assemblies of 1-methyllumazine-6-carboxylic acid, an amino acid residue and anthranilic acid methyl ester connected by peptide bonds. These new compounds exhibited pharmacological activity by improving insulin sensitivity, which was evaluated in an adipogenesis model using human bone marrow mesenchymal stem cells. In addition, the compounds exhibited fluorescence changes upon binding to DNA, demonstrating their potential applications to DNA sequence recognition.

Depth profiling of epidermal hydration inducing improvement of skin roughness and elasticity: in vivo study by confocal Raman spectroscopy.

INTRODUCTION: Skin hydration in the stratum corneum plays an important role in skin condition, and skin efficacy properties are influenced by its hydration level. However, few studies have identified the correlation between changes in skin hydration content and skin characteristics by skin depth level. AIMS: This study aims to determine how changes in skin hydration at specific depth levels affect skin condition by long-term tracking changes in hydration of stratum corneum and viable epidermis after usage of moisturizer. METHODS: Ten volunteers were recruited and subjected to in vivo confocal Raman spectroscopy to perform water content profiling at skin depths of up to 52 µm. Mechanical properties of skin were measured using Cutometer and Antera 3D. Skin-elasticity and roughness values observed before and after 15 days of moisturizing emulsion use were compared to demonstrate the correlation between observed changes in skin efficacy parameters and skin water content at specific depths. RESULTS: Significant increase in relative water content at specific depths was observed in this study. Among mechanical properties of skin, only R4, R6, and R8 parameters demonstrated significant changes. Additionally, rates of change in values of the R6 and R8 parameters revealed a high correlation with water content changes at viable epidermis depths below the stratum corneum. On the other hand, skin roughness parameter showed a correlation with water content changes at the outermost layer of stratum corneum. CONCLUSION: Results of this study indicate that skin elasticity is influenced by its hydration level at viable epidermis depths and skin roughness at stratum corneum each. This suggests that monitoring depth profiles of water content using in vivo confocal Raman spectroscopy provides a breakthrough in tracking the skin efficacy effect of topically applied substances.

When Indolizine Meets Quinoline: Diversity-Oriented Synthesis of New Polyheterocycles and Their Optical Properties.

Fluorescence-based technologies play a pivotal role in various biomedical applications. Here we report an efficient route to a new class of fluorophores, indolizino[3,2-c]quinolines, via the oxidative Pictet-Spengler cyclization strategy. The condensation of several 2-methylpyridines with 2-bromo-2'-nitroacetophenone allowed for the rapid assembly of indolizines with a 2-nitrophenyl group at the C2 position. The subsequent reduction of the nitro group under mild conditions followed by oxidative Pictet-Spengler cyclization with various aryl aldehydes in the presence of a catalytic amount of FeCl3 furnished the indolizino[3,2-c]quinolines in good overall yields. We also examined the photophysical properties of this new series of polyheterocyclic compounds. Several indolizino[3,2-c]quinolines were found to have unique and desirable optical properties, suggesting that these compounds may be suitable for use as prospective fluorescent probes in aqueous systems.

Novel C6-substituted 1,3,4-oxadiazinones as potential anti-cancer agents.

The insulin-like growth factor 1 receptor (IGF-1R) is a membrane receptor tyrosine kinase over-expressed in a number of tumors. However, combating resistance is one of the main challenges in the currently available IGF-1R inhibitor-based cancer therapies. Increased Src activation has been reported to confer resistance to anti-IGF-1R therapeutics in various tumor cells. An urgent unmet need for IGF-1R inhibitors is to suppress Src rephosphorylation induced by current anti-IGF-1R regimens. In efforts to develop effective anticancer agents targeting the IGF-1R signaling pathway, we explored 2-aryl-1,3,4-oxadiazin-5-ones as a novel scaffold that is structurally unrelated to current tyrosine kinase inhibitors (TKIs). The compound, LL-2003, exhibited promising antitumor effects in vitro and in vivo; it effectively suppressed IGF-1R and Src and induced apoptosis in various non-small cell lung cancer cells. Further optimizations for enhanced potency in cellular assays need to be followed, but our strategy to identify novel IGF-1R/Src inhibitors may open a new avenue to develop more efficient anticancer agents.