Fatty Acid Composition, Tocopherols, Volatile Compounds, and Sensory Evaluation of Low Morphine Yielding Varieties of Poppy (Papaver somniferum L.) Seeds and Oils.

Low morphine yielding winter ('Zeno Morphex') and summer ('Viola', 'Mieszko', 'Borowski') poppy varieties were investigated for their chemical composition and sensory properties. The oil content of the 13 seed samples as well as that of fatty acids, tocopherols, and volatile compounds in the respective oils were determined, and the sensory profiles of the seeds and oils were established. Linoleic acid made up 70.7-75.2% of the fatty acids. High amounts of γ-tocopherol were detected, especially in variety 'Viola' (287 ± 34 mg kg-1), while δ-tocopherol was only present in 'Zeno Morphex' (3.9 ± 0.6 mg kg-1). The most abundant volatiles were caproic acid (1.4-148 µg g-1), hexanal (0.9-15.2 µg g-1), 1-hexanol (0.3-20.1 µg g-1), limonene (1.3-9.4 µg g-1), and 2-pentylfuran (1.0-7.8 µg g-1). The sensory panel distinguished samples in particular by fatty/oily, rancid, sweet, and green attributes, the green aroma being correlated to three methoxypyrazines only present in summer poppies.

A series of novel aryl-methanone derivatives as inhibitors of FMS-like tyrosine kinase 3 (FLT3) in FLT3-ITD-positive acute myeloid leukemia.

Mutants of the FLT3 receptor tyrosine kinase (RTK) with duplications in the juxtamembrane domain (FLT3-ITD) act as drivers of acute myeloid leukemia (AML). Potent tyrosine kinase inhibitors (TKi) of FLT3-ITD entered clinical trials and showed a promising, but transient success due to the occurrence of secondary drug-resistant AML clones. A further caveat of drugs targeting FLT3-ITD is the co-targeting of other RTKs which are required for normal hematopoiesis. This is observed quite frequently. Therefore, novel drugs are necessary to treat AML effectively and safely. Recently bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. In order to optimize these agents we synthesized novel derivatives of these methanones with various substituents. Methanone 16 and its carbamate derivative 17b inhibit FLT3-ITD at least as potently as the TKi AC220 (quizartinib). Models indicate corresponding interactions of 16 and quizartinib with FLT3. The activity of 16 is accompanied by a high selectivity for FLT3-ITD.