Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents was written by Zhang, Xin-Hui;Bo-Wang;Tao, Yuan-Yuan;Ma, Qin;Wang, Hao-Jie;He, Zhang-Xu;Wu, Hui-Pan;Li, Yi-Han;Zhao, Bing;Ma, Li-Ying;Liu, Hong-Min. And the article was included in European Journal of Medicinal Chemistry in 2020.Application of 91-02-1 This article mentions the following:
A series of thiosemicarbazone derivatives I [R1 = H, 4-MeO, 2-Br, 3-Br, 4-Br; R2 = H, Me, 2-pyridyl, etc.; R3 = 2-furyl, 3-indolyl, 2-pyridyl, etc.; n = 0, 1, 2] containing different aromatic heterocyclic groups was synthesized and the tridentate donor system of the lead compound was optimized. Most of the target compounds I showed improved antiproliferative activity against MGC803 cells. SAR studies revealed that compound I [R1 = 4-MeO, R2 = Me, R3 = 2-pyridyl, n = 0] displayed significant advantages in inhibition effect with an IC50 value of 0.031μM, and better selectivity between cancer and normal cells than 3-AP and DpC (about 15- and 5-fold improved resp.). Besides, compound I [R1 = 4-MeO, R2 = Me, R3 = 2-pyridyl, n = 0] showed selective antiproliferative activity in not only other cancer cells but also different gastric cancer cell lines. In-depth mechanism studies showed that compound I [R1 = 4-MeO, R2 = Me, R3 = 2-pyridyl, n = 0] could induce mitochondria-related apoptosis which might be related to the elevation of intracellular ROS level, and cause cell cycle arrest at S phase. Moreover, compound I [R1 = 4-MeO, R2 = Me, R3 = 2-pyridyl, n = 0] could evidently suppressed the cell migration and invasion by blocking the EMT (epithelial-mesenchymal transition) process. Consequently, our studies provided a lead optimization strategy of thiosemicarbazone derivatives I which would contribute to discover high-efficiency and low-toxicity agents for the treatment of gastric cancer. In the experiment, the researchers used many compounds, for example, Phenyl(pyridin-2-yl)methanone (cas: 91-02-1Application of 91-02-1).
Phenyl(pyridin-2-yl)methanone (cas: 91-02-1) belongs to pyridine derivatives. Pyridine is diamagnetic and has a diamagnetic susceptibility of −48.7 × 10−6 cm3·mol−1.The molecular electric dipole moment is 2.2 debyes. The standard enthalpy of formation is 100.2 kJ·mol−1 in the liquid phase and 140.4 kJ·mol−1 in the gas phase. Many analogues of pyridine are known where N is replaced by other heteroatoms . Substitution of one C–H in pyridine with a second N gives rise to the diazine heterocycles (C4H4N2), with the names pyridazine, pyrimidine, and pyrazine.Application of 91-02-1