Chun Lei,Wanjing Yang,Ziyu Lin,Yuyan Tao,Renping Ye,Yucai Jiang,Yuli Chen,Beidou Zhou
Four benzophenones, three dihydrocoumarins, and two coumarins were synthesised by a 1–3 step reaction, with yields ranging from 6.2 to 35%. Next, we investigated the in vitro antitumour activity of these compounds. Compounds 1, 8, and 9 exhibited strong antitumour activity and were considered promising candidates in this field. In particular, compound 1 exhibited very strong inhibitory activity against HL-60, A-549, SMMC-7721, and SW480 cells, with IC50 values of 0.48, 0.82, 0.26, and 0.99 μM, respectively. Finally, the antitumour mechanism of compound 1 was investigated through network pharmacology and molecular docking analyses, which identified 22 key genes and 21 tumour pathways. AKT1, ALB, CASP3, ESR1, GAPDH, HSP90AA1, and STAT3 were considered as potential target hub genes for compound 1. These results will enable the future development of benzophenone and its derivatives.
Jiahe Fan,Chaoyi Lv,Zhizhou Li,Mengru Guo,Yichen Yin,Hui Wang,Wei Wang,Shiwei Sun
α-Glucosidase is the key enzyme on carbohydrate metabolism, and its bioactive inhibitors are supposed to be an effective therapeutic for type 2 diabetes mellitus. During our continuing study for discovering α-glucosidase inhibitors, a fungus GDZZ-G2 which is derived from a medicinal plant Callicarpa kwangtungensis Chun, exhibited significant inhibition on α-glucosidase. The strain was identified as Fusarium incarnatum by morphological and molecular methods. Further bioassay-guided fractionation result in six known secondary metabolites ( 1 - 6 ). All the compounds except 4 were isolated from F . incarnatum for the first time. Among them, an anthraquinonoid ( S )-1,3,6-trihydroxy-7-(1-hydroxyethyl)anthracene-9,10-dione (compound 1 ) exhibited strong inhibitory effect against α-glucosidase (IC 50 = 77.67 ± 0.67 μΜ), compared with acarbose (IC 50 = 711.8 ± 5 μΜ). An enzyme kinetics analysis revealed that compound 1 was an uncompetitive inhibitor. Besides, docking simulations predicted that compound 1 inhibited α-glucosidase substrate complex by binding Gln322, Gly306, Thr307, and Ser329 through hydrogen-bond interactions. Our findings suggested that compound 1 can be considered a lead compound for further modifications and the development of a new effective drug candidate in the treatment of type 2 diabetes mellitus.
危险品化学品经营许可证（带存储）