Identification of New Purpuroine Analogues from the Arctic Echinodermata Pteraster militaris That Inhibit FLT3-ITD+ AML Cell Lines

Isolation of bioactive products from the marine environment is considered a very promising approach to identify new compounds that can be used for further drug development. In this work we have isolated three new compounds from the purpuroine family by mass-guided preparative HPLC; purpuroine K-M. These compounds where screened for antibacterial- and antifungal activity, antibiofilm formation and anti-cell proliferation activity. Additionally, apoptosis-, cell cycle-, kinase binding- and docking studies were performed to evaluate the mechanism-of-action. None of the compounds showed activity in antibacterial-, antibiofilm- or antifungal assays. However, one of the isolated compounds, purpuroine K, showed activity against two cell lines, MV-4-11 and MOLM-13, two AML cell lines both carrying the FTL3-ITD mutation. In MV-4-11 cells, purpuroine K was found to increase apoptosis and arrest cells cycle in G1/G0, which is a common feature of FLT3 inhibitors. Interactions between purpuroine K and the FLT3 wild type or FLT3 ITD mutant proteins could however not be elucidated in our kinase binding and docking studies. In conclusion, we have isolated three novel molecules, purpuroine K-M, one of which (purpuroine K) shows a potent activity against FLT3-ITD mutated AML cell lines, however, the molecular target(s) of purpuroine K still need to be further investigated.     

Performance of wild Saccharomyces and Non-Saccharomyces yeasts as starter cultures in dough fermentation and bread making

The use of wild Saccharomyces and non-Saccharomyces yeasts might result in bread with different and attractive sensory characteristics. This study aimed to evaluate the performance of Saccharomyces and non-Saccharomyces yeasts as starter culture in dough fermentation to bread making and the physicochemical parameters and aromatic profile of bread. All 26 wild yeasts strains isolated from Brazilian Cerrado fruit and tree bark were osmotolerant, and 19.4% were able to ferment maltose. Candida tropicalis ART101.3 and Saccharomyces cerevisiae SC5952 had the best growth capacity under high concentrations of glucose and maltose. Also, they were resistant to lyophilisation. Kinetic parameters of bioreactor cultivations showed high cell growth and lower generation time with 10 g L⁻¹ maltose. Bread produced with C. tropicalis ART101.3 and the control bread had similar physicochemical properties and acceptance of consumers. Bread with S. cerevisiae SC5951 had a lower specific volume and a different colour than control bread; however, the consumers found no significant difference. More than 70% of the consumers demonstrated purchase intention of bread produced with both wild yeasts. The present study shows the potential of native Cerrado yeasts to be used and exploited in industrial processes and contributes to the diversification of bread starter cultures.