Unveiling the potential biochemical effects of selected heterocyclic compounds as human Type-A γ-aminobutyric acid (GABA A) Modulator: An Insilico Approach

Q1 Immunology and Microbiology

Biotechnology Reports Pub Date : 2025-04-11 DOI:10.1016/j.btre.2025.e00894

Abel Kolawole Oyebamiji , Sunday Adewale Akintelu , Oluwakemi Ebenezer , Faith Eniola Olujinmi , David O. Adekunle , Adesoji Alani Olanrewaju , Omowumi Temitayo Akinola , Samson Olusegun Afolabi , Ehimen Anastasia Erazua , Ayodeji Arnold Olaseinde

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引用次数: 0

Abstract

Background

Investigating the bioactivities of zuranolone derivatives as Type-A γ-aminobutyric acid inhibitors which will thereby down-regulate postpartum depression is considered a crucial study.

Method

This study is aimed at investigating the biochemical activities of 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3‑hydroxy-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile derivatives against type-A γ-aminobutyric acid (GABA A) which will thereby enhance the activity of γ-aminobutyric acid (GABA) in human central nervous system.

Results

In this work, series of computational tools such as Spartan 14, molecular operating environment software, Gromacs and Admetsar1 were explored and the studied compounds were subjected to this software which resulted to series of results. Vacuum was observed to have highest influence on highest occupied molecular orbital (E_H) of compound 1 and water as well as ethanol reduces its ability to donate electron to the nearby molecules. Also, the effect of water and ethanol were investigated on the studied compound via lowest unoccupied molecular orbital (E_L) and energy gap and the results were reported appropriately. The molecular docking investigation was carried out on the studied compounds and Type-A γ-aminobutyric acid (pdb id: 4cof) and the compounds 3 with calculated binding affinity value of -7.32433319kcal/mol as well as pi-H as the non-bonding interaction were observed which therefore confirm the potential ability of compound to inhibit the target than other studied compound. Also, compound 1 and reference compound were subjected to molecular dynamic simulation study and the actual binding energy for the selected compounds were obtained and reported.

Conclusion

Our findings from this work may open door for the design of several 1-(2-((3R,5R,8R,9R,10S,13S,14S,17S)-3-(benzyloxy)-3,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxoethyl)-1H-pyrazole-4-carbonitrile derivatives as potential Type-A γ-aminobutyric acid inhibitors.

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揭示选定的杂环化合物作为人A型γ-氨基丁酸（GABA A）调节剂的潜在生化作用：一种Insilico方法

研究祖拉诺酮类衍生物作为a型γ-氨基丁酸抑制剂的生物活性，从而降低产后抑郁被认为是一项至关重要的研究。方法研究1-（2-（(3R,5R,8R,9R,10S,13S,14S,17S)-3‑羟基-3,13-二甲基十六氢- 1h -环五[a]菲-17-基）-2-氧乙基）- 1h -吡唑-4-碳腈衍生物对γ-氨基丁酸（GABA）的生化活性，从而提高γ-氨基丁酸（GABA）在人中枢神经系统中的活性。结果研究了Spartan 14、分子操作环境软件、Gromacs、Admetsar1等一系列计算工具，并对所研究的化合物进行了处理，得到了一系列结果。真空对化合物1的最高已占据分子轨道（EH）影响最大，而水和乙醇降低了其向附近分子提供电子的能力。同时，通过最低未占据分子轨道（EL）和能隙考察了水和乙醇对化合物的影响，并对结果进行了相应的报道。对所研究的化合物与a型γ-氨基丁酸（pdb id: 4cof）进行了分子对接研究，并观察到化合物3的结合亲和值为-7.32433319kcal/mol和pi-H作为非键相互作用，从而证实了该化合物比其他所研究的化合物具有潜在的抑制靶标的能力。并对化合物1和参比化合物进行了分子动力学模拟研究，得到并报道了所选化合物的实际结合能。结论本研究结果为设计几种1-(2-（（3R,5R,8R,9R,10S,13S,14S,17S)-3-（苯氧基）-3,13-二甲基十六氢- 1h -环五[a]菲-17-基）-2-氧乙基）- 1h -吡唑-4-碳腈衍生物作为潜在的a型γ-氨基丁酸抑制剂打开了大门。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology Reports Immunology and Microbiology-Applied Microbiology and Biotechnology

CiteScore

15.80

自引率

0.00%

发文量

审稿时长

55 days

期刊介绍： Biotechnology Reports covers all aspects of Biotechnology particularly those reports that are useful and informative and that will be of value to other researchers in related fields. Biotechnology Reports loves ground breaking science, but will also accept good science that can be of use to the biotechnology community. The journal maintains a high quality peer review where submissions are considered on the basis of scientific validity and technical quality. Acceptable paper types are research articles (short or full communications), methods, mini-reviews, and commentaries in the following areas: Healthcare and pharmaceutical biotechnology Agricultural and food biotechnology Environmental biotechnology Molecular biology, cell and tissue engineering and synthetic biology Industrial biotechnology, biofuels and bioenergy Nanobiotechnology Bioinformatics & systems biology New processes and products in biotechnology, bioprocess engineering.