Fig. 1 SAR study of glabridin and subsequent structural modifications improve in vivo weight loss effect and chemical stability of the structural analogues. a Schematic of the development of HSG4112 from glabridin. b-d HFD-induced obese mice (n = 4 for all obese groups and n = 2 for the vehicle group) were orally administered with 150 mg·kg-1 of respective glabridin derivatives for 4 to 6 weeks in b hydrogenation, c etherification, and d chain elongation steps. Data represent mean only, without statistical analysis, due to low sample size specifically employed for the purpose of screening. e HFD-induced obese mice (n = 5) were orally administered with 50 mg·kg-1 of (R)-, (S)-, or racemic HSG4112 for 6 weeks for the enantiomerization step. Data represent mean ± SEM. Two-way ANOVA with Dunnett’s multiple comparison test was performed; *P < 0.05, **P < 0.01, ***P < 0.001 vs. Vehicle group. f, g Degradation of glabridin and HSG4112 was measured by HPLC in f acidic solution (1% HCl in MeOH) and in g basic solution (1% NaOH in MeOH). Data represent mean ± SD; error bar is not visible because of negligible deviance. Student’s t-test was performed; ***P < 0.001 vs. glabridin.