1-piperazine indole hybrid with nicotinic amide and nicotinic acid and their analogues 的一些药代动力学、安全性、生物活性的硅学预测和分子对接研究。

IF 2.3 Q2 MEDICINE, GENERAL & INTERNAL SAGE Open Medicine Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI:10.1177/20503121241274212
Melese Legesse Mitku, Abera Dessie Dagnaw, Derso Teju Geremew, Yeniewa Kerie Anagaw, Minichil Chanie Worku, Liknaw Workie Limenh, Yabibal Berie Tadesse, Asrat Elias Ergena
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引用次数: 0

摘要

背景:目前,在药物发现和设计过程中,人们在药物发现之初就利用硅学预测来评估化合物的物理化学、药代动力学和安全性。这种对化合物的物理化学、药代动力学和安全性的早期评估有助于研究人员将时间和资源仅投入到最有前景的先导化合物上,从而淘汰成功几率较低的化合物:本研究的目的是通过采用硅学预测策略,探索从 1-哌嗪吲哚杂环与烟碱酰胺和烟碱酸类似物中设计出的一种针对布氏锥虫磷酸果糖激酶的有前景的先导化合物,以提高其抗锥虫病活性:利用ADMETlab 2.0、ACD labs Chem Sketch软件14.0版、Molinspiration软件和MolPredictX在线工具预测了这些分子的理化性质、安全性、药代动力学和生物活性。结果表明,一些有潜力的候选化合物表现出了良好的特性。根据 Molinspiration 软件,烟酸和烟酸酰胺衍生物都显示出较高的激酶抑制剂活性,所有烟酸衍生物都显示出酶抑制剂和 GPCR 配体活性。根据 MolPredictX 在线工具,生物活性最高的衍生物是 NA-4、NA-11 和 NAD-11:总之,我们的研究结果为了解这些化合物的潜在功效和安全性提供了宝贵的见解。看来几乎所有化合物都成功通过了药代动力学评估,而且就某些生物活性而言,将烟酸整合到吲哚中似乎比烟酸酰胺更有益。
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In silico prediction of some pharmacokinetic, safety, biological activity and molecular docking studies of 1-piperazine indole hybrid with nicotinic amide and nicotinic acid and their analogues.

Background: In silico predictions are now being utilized in drug discovery and design to assess the physicochemical, pharmacokinetics, and safety properties of compounds at the beginning of the drug discovery process. This early evaluation of the physicochemical, pharmacokinetics, and safety properties of compounds helps the researchers to invest their time and resources only in the best prospective lead compounds by eliminating compounds with a low chance of success.

Objective: The purpose of this study was to explore a promising lead compound designed from 1-piperazine indole hybrid with nicotinic amide and nicotinic acid analogs targeted on Trypanosoma brucei phosphofructokinase for Trypanosomiasis activity by using in silico predictions strategy.

Results: The physicochemical, safety, pharmacokinetic, and biological activity properties of those molecules were predicted by using ADMETlab 2.0, ACD labs Chem Sketch software version 14.0, Molinspiration software, and MolPredictX online tool. Our results indicate that several promising candidates exhibit favorable characteristics. Based on Molinspiration software both nicotinic acid and nicotinic amide derivatives showed higher kinase inhibitor activity and all nicotinic acid derivatives revealed enzyme inhibitors and GPCR ligand activity. According to the MolPredictX online tool, the most biologically active derivatives were NA-4, NA-11, and NAD-11.

Conclusion: Overall, our findings offer valuable insights into the potential efficacy and safety of these compounds. It appears that almost all of the compounds have successfully passed the pharmacokinetic evaluations and integration of nicotinic acid into indole appears to be more beneficial than nicotinic amide regarding certain biological activities.

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来源期刊
SAGE Open Medicine
SAGE Open Medicine MEDICINE, GENERAL & INTERNAL-
CiteScore
3.50
自引率
4.30%
发文量
289
审稿时长
12 weeks
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