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parabens 对人类和老鼠胎盘3β-基固醇脱酶异型的作用:结构活性关系和对接分析

Jie Xiang¹, Mingzhu Zhong¹, Qian Zhang¹

¹Department of Obstetrics and Gynecology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.

The Journal of steroid biochemistry and molecular biology

|November 20, 2024

概括

常见的防腐剂帕拉本抑制人类胎盘3β-基固醇脱酶1型 (h3β-HSD1),影响类固醇生成. 它们的效力取决于结构特征,如碳链长度.

科学领域:

内分泌学在内分泌学.
药理学药理学是指药理学的学科.
毒理学毒理学毒理学

背景情况:

烯是消费品中广泛使用的防腐剂.
帕拉本的潜在内分泌干扰,特别是影响胎盘类固醇生成,是一个越来越令人担忧的问题.
对于对关键类固醇酶的帕拉本抑制的精确机制和结构-活性关系仍然不完全理解.

研究的目的:

调查各种类对人类胎盘3β-基固醇脱酶1型 (h3β-HSD1) 和其大鼠同类 (r3β-HSD4) 的抑制作用.
阐明抑制的机制,并探索对的结构-活性关系 (SAR),以了解它们对3β-HSD活性的影响.
评估对胎盘细胞中孕激素分泌的帕拉本暴露的功能影响.

主要方法:

酶活性测定使用胎盘显微体和孕醇作为基质.
高性能液体染色学与双重质谱学 (HPLC-MS/MS) 结合用于孕激素量化.
抑制动力学,分子对接模拟和基于物理化学性质的结构-活性关系分析.

主要成果:

类化合物抑制了h3β-HSD1和r3β-HSD4,其中非类化合物表现出最高的强度 (IC50 = 4.17 μM).
抑制的特征是混合/非竞争性,并降低了 JAr 细胞中的孕激素分泌.
接研究揭示了与NAD+和类固醇结合部位的相互作用;抑制功效与LogP和碳链长度负相关.

结论:

类化合物有效抑制胎盘3β-HSD酶,表明潜在的内分泌干扰机制.
帕拉本的抑制功效受到其化学结构的显著影响,特别是基链长度和脂性 (LogP).
这些发现强调了在评估对生殖健康和类固醇生成的风险时考虑烯结构的重要性.

关键词:

在3β-HSD中.帕拉本类药物可以胎盘胎盘胎盘胎盘孕产妇使用的孕.孕激素 (Progesterone) 是一种激素.

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