Exploring molecular fragments for fraction unbound in human plasma of chemicals: a fragment-based cheminformatics approach.

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY SAR and QSAR in Environmental Research Pub Date : 2024-09-01 Epub Date: 2024-10-18 DOI:10.1080/1062936X.2024.2415602
S Banerjee, A Bhattacharya, I Dasgupta, S Gayen, S A Amin
{"title":"Exploring molecular fragments for fraction unbound in human plasma of chemicals: a fragment-based cheminformatics approach.","authors":"S Banerjee, A Bhattacharya, I Dasgupta, S Gayen, S A Amin","doi":"10.1080/1062936X.2024.2415602","DOIUrl":null,"url":null,"abstract":"<p><p>Fraction unbound in plasma (<i>f</i><sub>u,p</sub>) of drugs is an significant factor for drug delivery and other biological incidences related to the pharmacokinetic behaviours of drugs. Exploration of different molecular fragments for <i>f</i><sub>u,p</sub> of different small molecules/agents can facilitate in identification of suitable candidates in the preliminary stage of drug discovery. Different researchers have implemented strategies to build several prediction models for <i>f</i><sub>u,p</sub> of different drugs. However, these studies did not focus on the identification of responsible molecular fragments to determine the fraction unbound in plasma. In the current work, we tried to focus on the development of robust classification-based QSAR models and evaluated these models with multiple statistical metrics to identify essential molecular fragments/structural attributes for fractions unbound in plasma. The study unequivocally suggests various <i>N</i>-containing aromatic rings and aliphatic groups have positive influences and sulphur-containing thiadiazole rings have negative influences for the <i>f</i><sub>u,p</sub> values. The molecular fragments may help for the assessment of the <i>f</i><sub>u,p</sub> values of different small molecules/drugs in a speedy way in comparison to experiment-based in vivo and in vitro studies.</p>","PeriodicalId":21446,"journal":{"name":"SAR and QSAR in Environmental Research","volume":"35 9","pages":"817-836"},"PeriodicalIF":2.3000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"SAR and QSAR in Environmental Research","FirstCategoryId":"93","ListUrlMain":"https://doi.org/10.1080/1062936X.2024.2415602","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/18 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

Abstract

Fraction unbound in plasma (fu,p) of drugs is an significant factor for drug delivery and other biological incidences related to the pharmacokinetic behaviours of drugs. Exploration of different molecular fragments for fu,p of different small molecules/agents can facilitate in identification of suitable candidates in the preliminary stage of drug discovery. Different researchers have implemented strategies to build several prediction models for fu,p of different drugs. However, these studies did not focus on the identification of responsible molecular fragments to determine the fraction unbound in plasma. In the current work, we tried to focus on the development of robust classification-based QSAR models and evaluated these models with multiple statistical metrics to identify essential molecular fragments/structural attributes for fractions unbound in plasma. The study unequivocally suggests various N-containing aromatic rings and aliphatic groups have positive influences and sulphur-containing thiadiazole rings have negative influences for the fu,p values. The molecular fragments may help for the assessment of the fu,p values of different small molecules/drugs in a speedy way in comparison to experiment-based in vivo and in vitro studies.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
探索人体血浆中化学品未结合部分的分子片段:基于片段的化学信息学方法。
药物在血浆中的未结合分数(fu,p)是影响药物输送和其他与药物药代动力学行为相关的生物事件的一个重要因素。探索不同小分子/试剂在血浆中的未结合分数(fu,p)的不同分子片段,有助于在药物发现的初级阶段确定合适的候选药物。不同的研究人员已经实施了一些策略,建立了多个不同药物的药效预测模型。然而,这些研究并没有把重点放在识别负责的分子片段上,以确定血浆中未结合的部分。在目前的工作中,我们试图重点开发基于分类的稳健 QSAR 模型,并用多种统计指标对这些模型进行评估,以确定血浆中未结合部分的重要分子片段/结构属性。研究明确表明,各种含 N 的芳香环和脂肪族基团对 fu,p 值有积极影响,而含硫的噻二唑环对 fu,p 值有消极影响。与基于实验的体内和体外研究相比,分子片段有助于快速评估不同小分子/药物的 fu,p 值。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
审稿时长
>24 weeks
期刊介绍: SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.
期刊最新文献
Enhanced prediction of beta-secretase inhibitory compounds with mol2vec technique and machine learning algorithms. Structure-based drug design of pre-clinical candidate nanopiperine: a direct target for CYP1A1 protein to mitigate hyperglycaemia and associated microbes. Structure-based pharmacophore modelling for ErbB4-kinase inhibition: a systematic computational approach for small molecule drug discovery for breast cancer. A deep learning model based on the BERT pre-trained model to predict the antiproliferative activity of anti-cancer chemical compounds. Discovery of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agents: virtual screening and molecular dynamic studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1