Development and structure-activity relationship study of SHP2 inhibitor containing 3,4,6-trihydroxy-5-oxo-5H-benzo[7]annulene.

SHP2, a non-receptor protein tyrosine phosphatase encoded by PTPN11 gene, plays an important role in the cell growth and proliferation. Activating mutations of SHP2 have been reported as a cause of various human diseases such as solid tumors, leukemia, and Noonan syndrome. The discovery of SHP2 inhibitor can be a potent candidate for the treatment of cancers and SHP2 related human diseases. Several reports on a small molecule targeting SHP2 have published, however, there are limitations on the discovery of SHP2 phosphatase inhibitors due to the polar catalytic site environment. Allosteric inhibitor can be an alternative to catalytic site inhibitors. 3,4,6-Trihydroxy-5-oxo-5H-benzo[7]annulene 1 was obtained as an initial hit with a 0.097 µM of IC50 from high-throughput screening (HTS) study. After the structure-activity relationship (SAR) study, compound 1 still showed the most potent activity against SHP2. Moreover, compound 1 exerted good potency against SHP2 expressing 2D and 3D MDA-MB-468.

Electrochemical effect on bioleaching of arsenic and manganese from tungsten mine wastes using Acidithiobacillus spp.

Mine wastes from tungsten mine which contain a high concentration of arsenic (As) may expose many environmental problems because As is very toxic. This study aimed to evaluate bioleaching efficiency of As and manganese (Mn) from tungsten mine wastes using the pure and mixed culture of Acidithiobacillus ferrooxidans and A. thiooxidans. The electrochemical effect of the electrode through externally applied voltage on bacterial growth and bioleaching efficiency was also clarified. The obtained results indicated that both the highest As extraction efficiency (96.7%) and the highest Mn extraction efficiency (100%) were obtained in the mixed culture. A. ferrooxidans played a more important role than A. thiooxidans in the extraction of As whereas A. thiooxidans was more significant than A. ferrooxidans in the extraction of Mn. Unexpectedly, the external voltage applied to the bioleaching did not enhance metal extraction rate but inhibited bacterial growth, resulting in a reverse effect on bioleaching efficiency. This could be due to the low electrical tolerance of bioleaching bacteria. However, this study asserted that As and Mn could be successfully removed from tungsten mine waste by the normal bioleaching using the mixed culture of A. ferrooxidans and A. thiooxidans.