S-Dihydrodaidzein and 3-(1,3-benzoxazol-2-yl)-benzamide, Two New Potential β-estrogen Receptor Ligands with Anti-adipogenic Activity.

Background: The elucidation of molecular pathways associated with adipogenesis has evidenced the relevance of estrogen and estrogen receptor beta (ERβ). The positive effects of ERβ ligands on adipogenesis, energy expenditure, lipolysis, food intake, and weight loss, make ERβ an attractive target for obesity control. From ligand-based virtual screening, molecular docking, and molecular dynamic simulations, six new likely ERβ ligands (C1 to C6) have been reported with potential for pharmacological obesity treatment.

Objective: In this study, the effect of molecules C1-C6 on adipogenesis using the murine 3T3-L1 cell line was evaluated.

Methods: Cell viability was assessed by MTT assays. Lipid accumulation and gene expression were investigated by ORO staining and real-time quantitative RT-PCR experiments, respectively.

Results: Cell viability was not significantly affected by C1-C6 at concentrations up to 10 μM. Interestingly, treatment with 10 μM of C1 (S-Dihydrodaidzein) and C2 (3-(1,3-benzoxazol-2-yl)- benzamide) for 72 h inhibited adipocyte differentiation; moreover, ORO staining evidenced a reduced intracellular lipid accumulation (40% at day 7). Consistently, mRNA expression of the adipogenic markers, PPARγ and C/EBPα, was reduced by 50% and 82%, respectively, in the case of C1, and by 83% and 59%, in the case of C2.

Conclusion: Altogether, these results show the two new potential β-estrogen receptor ligands, C1 and C2, to exhibit anti-adipogenic activity. They could further be used as lead structures for the development of more efficient drugs for obesity control.