Ugwu Joy C, Ubah Chioma B, Lawrence Peculiar, Edim Moses M, N Mbim Elizabeth, Enyike Jonathan O, Edet Henry O
Department of Microbiology, University of Calabar, Calabar, Nigeria.
Department of Pure and Applied Chemistry, University of Calabar, Calabar, Nigeria.
Appl Biochem Biotechnol. 2025 Feb;197(2):847-872. doi: 10.1007/s12010-024-05051-w. Epub 2024 Sep 18.
Glutathione remains one of the most efficient antioxidant compounds in living systems, and the biological abilities of hydrazides have been well documented in literature. This study highlights the phytochemical constituents of garlic and the separation of the bioactive benzoic acid, 4-chloro- 1-(4-methoxyphenyl) hydrazide (BA4C) using gas chromatography-mass spectroscopy (GC-MS) technique. Preliminary phytochemical screening reveals the presence of alkaloids, saponins, flavonoids, tannins, terpenoids, steroids and phenols. Computationally, compound BA4C was optimized using the B3LYP/aug-cc-PVDZ DFT method. Spectroscopic studies of the compound involved analysis of the vibrational FT-IR frequencies and the modes of vibrations. Frontier molecular orbitals analysis records an energy gap of 4.3391 eV; NBO studies reveal that the compound has strong perturbation energies of 246 kcal/mol and 269 kcal/mol among its intramolecular interactions such as *C - C to *C - C and *C - C to *C - C, respectively. According to the visualization of non-covalent interactions, steric repulsions were observed at the core of the phenyl and benzene rings. However, other regions of the compound depict a significant balance of forces between steric repulsions and van der Waals forces. To significantly deduce the reducing power of compound BA4C, electrons were found to be highly localized at the methoxy and hydrazide moieties significantly implying their propensity to donate electrons to oxidized systems. Furthermore, ADMET analysis reveals that the compound has two hydrogen donors. Most significantly, the compound binds to NADPH dehydrogenase (5V4P) and glutathione reductase (1XAN) with binding energies of - 6.0 kcal/mol and - 8.0 kcal/mol showing considerable favourable binding feasibility as well as forming plural hydrogen bonds with the amino acid residues. Notably, BA4C was bonded at the active site of 1XAN, which implies the ability of the compound for the reduction of oxidized glutathione.
谷胱甘肽仍然是生物系统中最有效的抗氧化化合物之一，酰肼的生物学特性在文献中已有充分记载。本研究重点介绍了大蒜的植物化学成分，以及使用气相色谱 - 质谱联用（GC - MS）技术分离生物活性苯甲酸4 - 氯 - 1 - （4 - 甲氧基苯基）酰肼（BA4C）。初步植物化学筛选显示存在生物碱、皂苷、黄酮类、单宁、萜类、甾体和酚类。通过计算，使用B3LYP/aug - cc - PVDZ密度泛函理论（DFT）方法对化合物BA4C进行了优化。该化合物的光谱研究涉及对振动傅里叶变换红外（FT - IR）频率和振动模式的分析。前沿分子轨道分析记录的能隙为4.3391电子伏特；自然键轨道（NBO）研究表明，该化合物在其分子内相互作用（如C - C到C - C以及C - C到C - C）之间具有246千卡/摩尔和269千卡/摩尔的强微扰能量。根据非共价相互作用的可视化结果，在苯基和苯环的核心观察到空间排斥。然而，该化合物的其他区域显示出空间排斥和范德华力之间的显著力平衡。为了显著推断化合物BA4C的还原能力，发现电子高度定位于甲氧基和酰肼部分，这显著暗示了它们向氧化系统供电子的倾向。此外，药物代谢及毒性预测（ADMET）分析表明该化合物有两个氢供体。最重要的是，该化合物与NADPH脱氢酶（5V4P）和谷胱甘肽还原酶（1XAN）结合，结合能分别为 - 6.0千卡/摩尔和 - 8.0千卡/摩尔，显示出相当有利的结合可行性，并且与氨基酸残基形成多个氢键。值得注意的是，BA4C结合在1XAN的活性位点，这意味着该化合物具有还原氧化型谷胱甘肽的能力。
