以结构为基础的药物设计为导向,对雌激素受体结合剂的识别
Rojalini Samanta1, Kishanta Kumar Pradhan1, Debanjan Sen2
1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, 83521, India.
Molecular diversity
|June 8, 2023
概括
来自Datura sp. 的天然化合物 作为癌症治疗中的雌激素受体抑制剂,显示出有前途. 计算方法确定了一种新型化合物DL-50,具有有利的类似药物的特性,并有可能进行实验验证.
科学领域:
- 药用化学 医学化学
- 计算生物学 计算生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 癌症是全球主要的死亡原因,雌激素受体 (ERs) 是重要的治疗点.
- 植物化学物质是抗癌药物的丰富来源,而Datura sp. 提取物已经显示出潜在的ER抑制.
- 雌激素受体阳性癌症占癌症诊断的很大一部分.
研究的目的:
- 以计算方式选Datura sp.中的天然产品. 对于雌激素受体抑制活性.
- 识别和设计具有高结合亲和力和对雌激素受体有利的类似药物的新型化合物.
- 通过分子动力学模拟来评估潜在药物候选物的稳定性和结合能.
主要方法:
- 报告的Datura sp.的分子对接 自然产品对抗雌激素受体.
- 根据结合方向和对接分数来选择得分最高的化合物.
- 对化合物的分子动力学模拟和结合能计算.
- 基于知识的 de novo 设计和相似性选,用于新型连接体的开发.
主要成果:
- 一种特定的配体,[(1S,5R) -8-甲基-8-阿扎比赛克罗 [3.2.1] 八-3-] (2R) -3-氧-2-烯酸盐,显示了有利的分子动力学模拟结果和药物相似性.
- 设计的de novo配体DL-50表现出令人满意的结合亲缘关系,药物相似性和可接受的ADMET配置文件.
- DL-50还显示了合成可访问性的轻松性,表明其可用于进一步研究的可行性.
结论:
- 计算查和设计确定DL-50是一种有前途的新型抑制剂,向雌激素受体.
- 鉴定的化合物具有有利的药理学和药理动力学特性,需要进行实验性研究.
- 这项研究强调了Datura sp.的潜力. 在抗癌药物发现中使用自然产品和计算方法.
相关概念视频
Transducer Mechanism: Nuclear Receptors
1.4K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.4K
Drug-Receptor Bonds
3.0K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
In...
3.0K
Structure-Activity Relationships and Drug Design
800
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
800
Ligand Binding Sites
7.8K
7.8K
G Protein-coupled Receptors
12.4K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
12.4K
Targets for Drug Action: Overview
6.5K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
6.5K


