Design, Synthesis and Pharmacological Evaluation of Naphthofuran Derivatives as Potent SIRT1 Activators.

ABSTRACT: Diabetic nephropathy (DN) is one of the most important medical complications in diabetic patients, which is an essential cause of end-stage renal disease in diabetic patients and still lacks effective medicines. Silent information regulator 1 (SIRT1) is closely related to the occurrence and development of DN. Activation of SIRT1 could significantly improve the symptoms of DN, while the activities of SIRT1 activators need to be further improved. Based on the crystal structure of SIRT1, structure and ligand-based approaches were carried out, and a lead compound 4,456-0661 (renamed as M1) was identified. Moreover, seven M1 analogues (6a-6g) were designed using a structure-based drug design strategy followed by bioactivity evaluation with SRTR2104 used as positive drugs. Among the target molec

SUBMITTER: Gao J 

PROVIDER: S-EPMC8113817 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature