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通过分子动力学建模方法研究来自海洋海藻代谢物的新型宫颈癌治疗药物。

Investigating new drugs from marine seaweed metabolites for cervical cancer therapy by molecular dynamic modeling approach.

作者信息

Islam Sk Injamamul, Ahmed Sheikh Sunzid, Mahfuj Sarower, Das Gunjan, Tareq Md Mohaimenul Islam, Almehmadi Mazen, Allahyani Mamdouh, Alsiwiehri Naif, Biswas Partha, Hasan Md Nazmul, Ahammad Foysal

机构信息

BioMac Lab, Dhaka, Bangladesh.

Department of Botany, Faculty of Biological Sciences, University of Dhaka, Dhaka, 1000, Bangladesh.

出版信息

Sci Rep. 2025 Jan 31;15(1):3866. doi: 10.1038/s41598-024-82043-0.

Abstract

The etiology of cervical cancer in women is attributed to the continuous infection of the human papillomavirus (HPV). The high costs and side effects of standard treatments and the limited efficacy of HPV vaccination have led to a quest for novel, cost-effective cervical cancer treatments, particularly in middle- and low-income countries. Therefore, our objective was to evaluate the capacity of marine seaweed compounds to hinder the activity of the cervical cancer E6 Oncoprotein. The Seaweed Metabolite Database was evaluated for its ability to inhibit E6 Oncoprotein functions by high throughput virtual screening. The investigations included molecular docking, ADMET test, MD simulation, and MM/GBSA analysis to identify three lead seaweed drug-like compounds: BC008 (-8.9 kcal/mol), RL379 (-8.9 kcal/mol), and BC014 (-8.7 kcal/mol). All of the leading candidates had positive characteristics in terms of pharmacokinetics, pharmacodynamics, and toxicity. The molecular dynamics simulation of the apoprotein, control drug, and lead compounds revealed the superior structural stability and uniformity of the main drug candidates. The MM/GBSA study revealed that the BC008-protein complex exhibited the most significant free binding energy, with a value of -57.41 kcal/mol. In the end, the findings derived from this investigation might provide a basis for developing innovative anticancer treatments.

摘要

女性宫颈癌的病因归因于人乳头瘤病毒(HPV)的持续感染。标准治疗的高成本和副作用以及HPV疫苗接种效果有限,促使人们寻求新型、具有成本效益的宫颈癌治疗方法,尤其是在中低收入国家。因此,我们的目标是评估海洋海藻化合物抑制宫颈癌E6癌蛋白活性的能力。通过高通量虚拟筛选评估了海藻代谢物数据库抑制E6癌蛋白功能的能力。研究包括分子对接、ADMET测试、分子动力学模拟和MM/GBSA分析,以确定三种潜在的类似海藻药物的化合物:BC008(-8.9千卡/摩尔)、RL379(-8.9千卡/摩尔)和BC014(-8.7千卡/摩尔)。所有主要候选物在药代动力学、药效学和毒性方面均具有积极特性。载脂蛋白、对照药物和主要化合物的分子动力学模拟揭示了主要药物候选物具有卓越的结构稳定性和一致性。MM/GBSA研究表明,BC008-蛋白质复合物表现出最显著的自由结合能,值为-57.41千卡/摩尔。最后,本研究结果可能为开发创新的抗癌治疗方法提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba9c/11785738/1a3d029cda3f/41598_2024_82043_Fig1_HTML.jpg

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