Design, synthesis and antitumor activity of 3-arenobufagin esters / 药学实践杂志

Objective To search for novel potent 3-ester derivatives of arenobufagin and test their antitumor activities in vitro. Methods Target compounds were synthesized by esterification of arenobufagin with acids. CellTiter method was used to assay the in vitro antitumor activities. Results 3-Ester derivatives exhibited excellent antitumor activities against all the cancer cells. Conclusion Among the 3-ester derivatives, compound 2a had the best activities with the IC50 of 4.0−91.7 nmol/L and appeared to be a valuable candidate for further study.

Discovery of bepridil as a valuable lead compound with potent p53-MDM2 inhibitory activity / 药学实践杂志

Objective To find novel lead compounds as p53-MDM2 inhibitors by drug repurposing strategy. Methods The p53-MDM2 inhibitory activities of compounds were determined by FP and western blotting. MTT method was used to determine the in-vitro antitumor activities. The metabolites in human liver microsomes were tested. Results Bepridil showed excellent in-vitro anti-tumor activity and strong p53-MDM2 protein binding inhibitory activity, which can significantly reduce the expression of MDM2 protein in a dose-dependent manner. The metabolites in human liver microsomes are mainly benzene ring hydroxyl mono-oxidation metabolites. Conclusion Bepridil can be used as a lead compound for p53-MDM2 protein binding small molecule inhibitors for subsequent structural optimization design studies.

Design, synthesis and biological activity of non-nucleoside NEDD8-activating enzyme inhibitors / 药学实践杂志

Objective To develop novel NAE inhibitors with non-nucleoside scaffold by a scaffold hopping strategy and study the in vitro antitumor activities. Methods Disulfonamideindazole 14 was synthesized through 23 steps with a good yield. Its chemical structure was confirmed by 1H NMR and MS. MTT method was used to determine the in vitro antitumor activities. Results Compound 14 exhibited moderate antitumor activities against various cancer cells and promoted significant UBC12 accumulation in a dose-dependent manner. Conclusion Compound 14 is a potent NAE inhibitor with remarkable apoptosis induction and cell cycle arrest in prostate cancer PANC-1 cells. Our work provides a valuable leading compound for the further design and development of NAE inhibitors.

Synthesis and hemostasis activity of iodine complex with carboxymethyl chitosan / 药学实践杂志

Objective To study the hemostasis activity of iodine complex with carboxymethyl chitosan .Methods The polymers were prepared with azodiisobutyronitrile as the initiating agent and sodium acrylate ,N‐vinylpyrrolidone ,carboxym‐ethyl chitosan and N ,N′‐methylene diacrylamide as the raw materials .It was then complexed with iodine to generate iodine complex with carboxymethyl chitosan ,and the hemostasis activity was tested at the same time .Results The polymers could absorb water with the value of 103g/g and showed potent hemostasis activity for auricular veins and femoral veins .Conclusion The results showed that hemostatic effect of polymers was better than that of hemostatic sponge and Quikclot .