对抗氧化剂和多克索鲁比辛组合的计算洞察力,用于有效的癌症治疗
Jyotsnamayee Nayak1, Seshu Vardhan P1, Suban K Sahoo1
1Department of Chemistry, S.V. National Institute of Technology, Gujarat, India.
Journal of biomolecular structure & dynamics
|August 7, 2023
概括
谷氨 (GSH) 和多克索鲁比辛 (DOX) 显示对拓酶-II具有对抗作用,可能影响癌症治疗. 此外,GSH还可以通过阻断DOX与环菲林D的结合来保护心脏,从而降低心脏毒性.
科学领域:
- 计算化学的计算化学
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 心脏病学 心脏病学
背景情况:
- 多克索鲁比 (DOX) 是一种强效的抗瘤剂,但会引起心脏毒性.
- 建议使用抗氧化剂来减轻DOX的副作用,但它们对疗效的影响仍在争论中.
- 托皮索马酶-II (Top-II) 和环菲林D (Cyp-D) 分别是癌症和心肌梗塞的关键标.
研究的目的:
- 研究DOX与抗氧化剂的in silico药理动力学和组合效应.
- 评估DOX和抗氧化剂与Top-II和Cyp-D的结合相互作用.
- 探索抗氧化剂降低DOX诱导心脏毒性的潜力.
主要方法:
- 对DOX和几个抗氧化剂 (美拉,NAC,GSH,β-胡卜素,维生素C) 进行了分子对接研究,针对Top-II和Cyp-D.
- 分子动力学 (MD) 模拟在最稳定的DOX和GSH与Cyp-D和Top-II.II的对接形态上进行了100 ns.
- 计算分析评估了结合亲和力,姿势和形状稳定性.
主要成果:
- 谷氨 (GSH) 对Top-II和Cyp-D活性位点表现出显著的结合亲和力.
- DOX强烈地与Top-II的DNA结合口袋结合,而GSH则占据了一个埋藏的地方.
- 结合GSH与Cyp-D有效地阻断了DOX的相互作用,这表明了对心脏毒性的保护机制.
结论:
- GSH和DOX的组合可能对Top-II产生对抗作用,因此需要进一步研究癌症治疗.
- 通过与Cyp-D的相互作用,GSH显示出抑制DOX诱导的心脏不良反应的潜力.
- 在的发现支持在DOX化疗期间探索GSH作为心脏保护剂.
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