Affiliation:
1. School of Parmacy and Pharmaceutical Sciences & Institute of Materia Medica Shandong First Medical University & Shandong Academy of Medical Sciences, NHC Key Laboratory of Biotechnology Drugs (Shandong Academy of Medical Sciences), Key Lab for Rare & Uncommon Diseases of Shandong Province Ji'nan Shandong 250117 China
2. School of Chemistry and Chemical Engineering, School of Biological Science and Technology University of Jinan Jinan China
3. Medical Science and Technology Innovation Center Shandong First Medical University & Shandong Academy of Medical Sciences Jinan China
Abstract
AbstractIn the literature, daidzein has been reported to exhibit cardiovascular protective effects and hypoglycemic activity in mice. We sought to design and synthesize a novel compound, SJ‐6, an analog of daidzein, with improved hypoglycemic properties. Although SJ‐6 demonstrated favorable hypoglycemic effects, its pharmacokinetic limitations prompted us to design and synthesize prodrugs of SJ‐6. We conducted a comprehensive evaluation of the prodrugs, including in vitro and in vivo studies, such as cytotoxicity, absorption, distribution, metabolism, excretion, and toxicity (ADMET) simulation analysis, in vitro blood–brain barrier (BBB) permeability evaluation, compound effect on insulin resistance, oral glucose tolerance test (OGTT), in vivo plasma concentration testing, acute toxicity test in rats, and long‐term gavage administration experiment. Furthermore, we examined the antidiabetic nephropathy activity of our lead compound, compound 10, which demonstrated superior efficacy compared with the positive control drug, metformin hydrochloride. Our findings suggest that compound 10 represents a promising lead compound for the prevention and treatment of diabetic nephropathy.
Subject
Drug Discovery,Pharmaceutical Science