芳酶作为人类和老鼠胎盘中的类甲的新目标:3D定量结构-活性关系和对接分析
Chaochao Gong1, Zhuoqi Chen2, Yunbing Tang2
1Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education; Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
某些类型的帕拉本可以抑制芳香酶 (CYP19A1),这种酶对雌激醇的产生至关重要. 这会影响雌激素生物合成,并可能影响生殖组织.
科学领域:
- 内分泌学 在内分泌学.
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
背景情况:
- 芳酶 (CYP19A1) 对于雌醇生物合成至关重要,主要在生殖组织中.
- 烯是常见的防腐剂,具有潜在的内分泌干扰作用.
- 了解帕拉本与CYP19A1的相互作用对于评估其生物影响至关重要.
研究的目的:
- 研究帕拉本酸和九种帕拉本对人类和老鼠芳酶 (CYP19A1) 活性的抑制作用.
- 为了评估这些类甲对人类胆瘤BeWo细胞中雌激素分泌的影响.
- 阐明抑制CYP19A1.1.的帕拉本背后的机制.
主要方法:
- 用人类和老鼠的胎盘显微体进行酶活性测定.
- 在BeWo细胞中测试雌激醇分泌量.
- 动力分析,定量结构-活性关系 (QSAR) 研究和分子对接.
主要成果:
- 基,丁基,基,基和非基 parabens 显著抑制了人类和老鼠的 CYP19A1 活性.
- 这些类甲降低了BeWo细胞中的雌激素分泌.
- 动力学分析显示混合抑制;QSAR和对接研究表明在血红素-铁结合部位的疏水性相互作用.
结论:
- 特定的类甲作为芳香酶 (CYP19A1) 的强有力的抑制剂.
- 抑制CYP19A1的帕拉本可以降低雌激醇生物合成.
- 这些发现提供了对的毒性及其潜在的内分泌干扰机制的见解.
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