S-去氢大豆苷元和 3-(1,3-苯并恶唑-2-基)苯甲酰胺，两种具有抗脂肪生成活性的新型潜在的β-雌激素受体配体。

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

机构信息

Laboratorio de Biomedicina Molecular 2, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional, Guillermo Massieu Helguera No. 239, La Escalera Ticoman, 07320, Ciudad de México, México.

Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Calle San Lorenzo 290, Col. del Valle Sur, Benito Juárez, 03100, Ciudad de México, México.

出版信息

Med Chem. 2024;20(4):434-442. doi: 10.2174/0115734064285786231230185457.

DOI:10.2174/0115734064285786231230185457

PMID:38192145

Abstract

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.

摘要

背景

与脂肪生成相关的分子途径的阐明表明了雌激素和雌激素受体β（ERβ）的相关性。ERβ配体对脂肪生成、能量消耗、脂肪分解、食物摄入和体重减轻的积极影响，使 ERβ 成为肥胖控制的一个有吸引力的靶点。通过基于配体的虚拟筛选、分子对接和分子动力学模拟，已经报道了六种新的可能的 ERβ 配体（C1 到 C6），具有治疗肥胖症的药理学潜力。

目的

本研究评估了分子 C1-C6 对使用小鼠 3T3-L1 细胞系的脂肪生成的影响。

方法

通过 MTT 测定法评估细胞活力。通过 ORO 染色和实时定量 RT-PCR 实验分别研究脂质积累和基因表达。

结果

在高达 10 μM 的浓度下，C1-C6 对细胞活力没有显著影响。有趣的是，用 10 μM 的 C1（S-二氢大豆苷元）和 C2（3-（1,3-苯并恶唑-2-基）苯甲酰胺）处理 72 小时抑制脂肪细胞分化；此外，ORO 染色表明细胞内脂质积累减少（第 7 天减少 40%）。一致地，C1 使脂肪生成标志物 PPARγ 和 C/EBPα 的 mRNA 表达分别降低 50%和 82%，C2 使它们分别降低 83%和 59%。