Minnamide A is a lipopeptide with a unique repeating structure consisting of hydroxy and proposed β-branched methyl groups. The absolute configuration of minnamide A was determined by a combination of chemical degradation, chiral HPLC analyses, and synthetic methods. Minnamide A showed growth-inhibitory activity toward HeLa cells with an IC50 value of 0.17 μM and rapidly induced cell death at a concentration of 2 μM. Minnamide A induced the copper-mediated accumulation of reactive oxygen species.
The synthesis of two marine lipodipeptides, majusculamides A and B, is described. The key feature of this synthesis is the stereoselective construction of an α-methyl-β-keto-carboxamide moiety.
Abstract Nobiletin is a unique flavonoid having polymethoxy groups and has exhibited anti‐inflammatory and antiobesity effects. Here, we examined the inhibition of nobiletin on melanogenesis induced by endothelin‐1 (ET) and stem cell factor (SCF) in normal human melanocytes. Nobiletin dose dependently reduced ET plus SCF‐stimulated tyrosinase activity without causing cytotoxicity. Nobiletin reduced cAMP‐response element‐binding protein (CREB) phosphorylation and microphthalmia‐associated transcription factor (MITF) expression, which is a key transcription factor for tyrosinase expression in pigmentation induced by ET plus SCF stimulation. Nobiletin treatment effectively decreased ET plus SCF‐induced Raf‐1, MEK and ERK1/2 phosphorylation and also downregulated the forskolin‐induced phosphorylation of CREB. Furthermore, nobiletin inhibited ET plus SCF‐triggered production of melanin and expression of MITF/tyrosinase in a three‐dimensional human epidermal model. In accordance with protein expression, the expression of genes related to the pigmentation was also increased in the cells stimulated with ET plus SCF and the cotreatment with nobiletin decreased obviously the ET plus SCF‐triggered gene expressions of tyrosinase, PMEL, TRP1 and MITF. Nobiletin contributes to hypopigmentation by downregulating MITF and tyrosinase expression through reduced Raf‐1 phosphorylation. Our findings implicate nobiletin as a potential new whitening agent.
Abstract New 13-epi-neoverrucosane-type diterpenes 1 and 2 were isolated from the marine sponge Axinyssa tethyoides. Their structures were elucidated by 2D-NMR spectroscopy, the modified Mosher’s method, and fluorescent X-ray analysis. 1 and 2 are the first 13-epi-neoverrucosane-type diterpenes that possess a sulfate group.
Two new pyrrolinone-containing lipopeptides, ypaoamides B (1) and C (2), were isolated from an Okeania sp. marine cyanobacterium collected in Okinawa. Their structures were determined by spectroscopic analysis and Marfey's analysis of acid hydrolysates. Ypaoamides B (1) and C (2) stimulated glucose uptake in cultured rat L6 myotubes. In particular, ypaoamide B (1) showed potent activity and activated AMP-activated protein kinase.
