Design, Synthesis, and Biological Evaluation of Novel Pyrrolo [2,3-b] Pyridine Derivatives for Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is featured with liver fat infiltration and accumulation with no connection with overdrinking. With the rising trends and no FDA-approved drugs, NAFLD attracts global attention. In this study, we successfully synthesized 18 novel SIS3 derivatives and evaluated them for pharmacological activity. F-9 and F-15 had potent weight-losing effects. Importantly, intraperitoneal administration of F-9 at 10 mg center dot kg(-1)center dot day(-1) for 5 weeks had the most excellent effects to reduce the weight of the body, liver, and fat, as well as adjusting serum levels of AST, ALT, TC, TG, HDL, and LDL. H&E staining showed that F-9 could suppress fat deposition and increase the adipocyte size in the liver.

Automated summary

In this study, we synthesized 18 novel SIS3 derivatives and found that F-9 and F-15 have weight-losing effects. Particularly, F-9 administered intraperitoneally at a dose of 10 mg/kg for 5 weeks showed the most excellent effects in reducing body weight, liver fat, and serum levels of AST, ALT, TC, TG, HDL, and LDL. H&E staining demonstrated that F-9 could suppress fat deposition and increase adipocyte size in the liver.