Methylation in hangtaimycin biosynthesis and its antibacterial activities.

About two-thirds of small molecule drugs contain methyl group and it plays a very important role in the drug development. So, methyltransferases catalyzing the methylation have always attracted great attention. Hangtaimycin (HTM) is a potent hepatoprotective agent. Previous study showed that its biosynthetic gene cluster contained three methyltransferase domains, but their characteristics in HTM biosynthetic pathway has not been revealed. In this study, we clarified multi-methylations in HTM biosynthesis in vivo. It showed that the two S-adenosylmethionine-dependent methyltransferases (SAM-MTs) of HtmA2(-module 6)-MT domain and HtmB2(-module 18)-MT domain are responsible for the installation of methyl group at C-45 and N-12, respectively, whereas the FK506 methyltransferase (FKMT) type O-methyltransferase of HtmB1(-module 16)-MT domain take care of the methylation at O-21 of HTM. We also reported the antibacterial activities of HTM in this study, and found that it showed activities against M. luteus, B. thuringiensis and A. baumannii with MIC of 4 µg/mL, 4 µg/mL, and 64 µg/mL, respectively.

A review: The nutrition components, active substances and flavonoid accumulation of Tartary buckwheat sprouts and innovative physical technology for seeds germinating.

Compared with the common grain, Tartary buckwheat enjoys higher nutritional value. Some distinctive nutrition associated with physiological activity of Tartary buckwheat is valuable in medicine. In addition, it's a good feed crop. In the paper, the main components (starch, protein, amino acid, fatty acid and mineral) and polyphenol bioactive components in Tartary buckwheat and its sprouts were reviewed, and the accumulation of flavonoids in sprouts during germination, especially the methods, synthetic pathways and mechanisms of flavonoid accumulation was summarized. The research on bioactive components and health benefits of Tartary buckwheat also were reviewed. Besides, the applications of innovative physical technology including microwave, magnetic, electromagnetic, ultrasonic, and light were also mentioned and highlighted, which could promote the enrichment of some active substances during seeds germination and growth of Tartary buckwheat sprouts. It would give a good support and benefit for the research and processing of Tartary buckwheat and its sprouts in next day.

Modification, Biological Evaluation and SAR Studies of Novel 1H-Pyrazol Derivatives Containing N,N'-Disubstituted Urea Moiety as Potential Anti-melanoma Agents.

Malignant melanomas are amongst the most aggressive cancers. BRAF Inhibitors have exhibited therapeutic effects against BRAF-mutant melanoma. In continuation of our earlier studies on anti-melanoma agents based on 1H-pyrazole skeleton, two sets of novel compounds that include 1H-pyrazole-4-amines FA1 - FA13 and corresponding urea derivatives FN1 - FN13 have been synthesized and evaluated for their BRAFV600E inhibitory and antiproliferation activities. Compound FN10 displayed the most potent biological activity against BRAFV600E (IC50 = 0.066 µm) and the A375 human melanoma cell line (GI50 = 0.81 µm), which was comparable to the positive control vemurafenib, and more potent than our previously reported 1H-pyrazole-3-amines and their urea derivatives. The results of SAR studies and molecular docking can guide further optimization and may help to improve potency of these pyrazole-based anti-melanoma agents.