Department of Biotechnology, Lyallpur Khalsa College, Jalandhar, India.
Curr Drug Discov Technol. 2022;19(6):e150622206033. doi: 10.2174/1570163819666220615142933.
Glucosinolates (β-thioglucoside-N-hydroxysulfates) are a water-soluble organic anion with sulfur- and nitrogen-containing glycosides which are found in abundance in Cruciferous plants. Ergosterol (ERG13) lanosterol-14α-demethylase protein has been targeted for inhibition studies as a key regulator enzyme of fungal membrane biosynthesis.
To understand the molecular mechanism of inhibition of Ergosterol (ERG13) lanosterol- 14α-demethylase by various phytochemicals from brassicales, i.e., glucosinolates and their potential role as putative drug molecules.
In this study, in silico analyses were performed to predict the molecular basis of various glucosinolates as a potential inhibitor of lanosterol-14α-demethylase protein, which is a key regulator of fungal membrane biosynthesis and its pharmacodynamics and toxicity profile. 3d structures of various glucosinolates were retrieved from PubChem, and the target protein, lanosterol-14α-demethylase (Pdb ID- 4lxj), was retrieved from the RCSB protein data bank. Molecular docking and interactions were carried out using the PyRx software using the AutoDOCK toolbar with default parameters. Dru- LiTo, ORISIS web servers were used to predict various drug likeliness predictions and Lipinski's Rule of 5, whereas admetSAR was used for prediction of toxicity, and PASS Program was used to study the antifungal and antimicrobial properties of these compounds.
This study shows that among the different compounds screened, gluconasturtiin, Glucotropaeolin, and Indolylmethyl-Glucosinolate showed the highest binding energies of -8.7 kcal/mol, -8.5 kcal/mol, and -8.3 kcal/mol with the lanosterol-14α-demethylase, respectively. Further all the compounds follow the Lipinski's rule as well as they are found to be non-carcinogenic and non-cytotoxic in nature. These compounds also show antifungal properties.
This study thus reveals that various glucosinolates interact with the ERG13 enzyme at various amino acid positions, which behaves as a catalytic site, thus indicates the probable mechanism of inactivation, and subsequently, these can be used as potential drug molecules. In vitro studies can be taken to further examine the utility of these compounds as antifungal agents.
硫代葡萄糖苷（β-硫代葡萄糖苷-N-羟磺酸盐）是一种富含十字花科植物的水溶性含硫和含氮的糖苷有机阴离子。麦角固醇 14α-脱甲基酶蛋白（ERG13）已被作为真菌膜生物合成的关键调节酶进行抑制研究。
了解各种来自 Brassicales 的植物化学物质（即硫代葡萄糖苷及其作为潜在药物分子的潜在作用）对麦角固醇 14α-脱甲基酶的抑制作用的分子机制。
在这项研究中，通过计算机模拟分析预测了各种硫代葡萄糖苷作为潜在的角鲨烯 14α-脱甲基酶蛋白抑制剂的分子基础，角鲨烯 14α-脱甲基酶蛋白是真菌膜生物合成的关键调节酶及其药效学和毒性特征。从 PubChem 中检索到各种硫代葡萄糖苷的 3d 结构，并从 RCSB 蛋白质数据库中检索到靶蛋白角鲨烯 14α-脱甲基酶（pdb ID-4lxj）。使用 PyRx 软件和 AutoDOCK 工具栏，使用默认参数进行分子对接和相互作用。使用 Dru-LiTo、ORISIS 网络服务器预测各种药物相似性预测和 Lipinski 的 5 规则，而 admetSAR 用于预测毒性，PASS 程序用于研究这些化合物的抗真菌和抗菌特性。
这项研究表明，在所筛选的不同化合物中，葡萄糖酸表告依春、葡萄糖替普、吲哚甲基硫代葡萄糖苷分别以-8.7 kcal/mol、-8.5 kcal/mol 和-8.3 kcal/mol 的最高结合能与角鲨烯 14α-脱甲基酶结合。此外，所有化合物都遵循 Lipinski 的规则，并且它们被发现是非致癌和非细胞毒性的。这些化合物也具有抗真菌特性。
因此，这项研究表明，各种硫代葡萄糖苷与 ERG13 酶在不同的氨基酸位置相互作用，这些位置表现为催化位点，从而表明了可能的失活机制，并且随后这些可以用作潜在的药物分子。可以进行体外研究进一步研究这些化合物作为抗真菌剂的用途。
