Synthesis of 2-methyl-5-methoxy-1,4-benzoquinone and In-silico Activity Profiling Toward Cytochrome P450-3A4

9th Annual Basic Science International Conference 2019

自然科学（总论）

Dwisari, Fath^1 ; Srihardyastutie, Arie^1 ; Ulfa, Siti Mariyah^1

Department of Chemistry, Faculty of Science, Brawijaya University, 65145, Indonesia^1

关键词: Activity profiling;    Cytochrome P450-3A4;    Drug candidates;    FTIR analysis;    Inhibitory concentration;    Lipophilicity;    Molecular docking;    Needle crystals;   

Others  :  https://iopscience.iop.org/article/10.1088/1757-899X/546/6/062005/pdf
DOI  :  10.1088/1757-899X/546/6/062005

学科分类：自然科学（综合）

来源: IOP

【 摘 要 】

The synthesis of 2-methyl-5-methoxy-1,4-benzoquinone (2) was carried out by reflux of 2-methyl-1,4-benzoquinone (1) with MeOH and ZnCl2 for 12 hours at ambient. The reaction resulted a yellow needle crystal in 6.92 % yield (m.p 173-175°C). The FT-IR analysis showed the presence of-OCH3 group at 1210 cm-1. The analysis using 1H-NMR showed chemical shift a δ = 3.81 ppm and the 13C-NMR gave 56.38 ppm for hydrogen and carbon from-OCH3 group. The bioavailability tests were determined by using in silico approach included lipophilicity (log P) and half maximum inhibitory concentration (IC50). It showed that the lipophilicity of 2 (log P = 0.92) is lower than 1 (log P = 1.79) which is calculated using Hyperchem software. The molecular docking of 2 towards cytochrome P450-3A4 showed a good result with IC50 13.68 ppm better than 1 (IC50 65.617 ppm). Further experimental is proposed for bromoalkylation of 2 using bromooctanoic acid to give 3-(7-bromoheptyl)-2-methyl-5-methoxy-1,4-benzoquinone (3). The in-silico calculation of 3 showed better lipophilicity (log P = 3.64) and IC50 (9.725 ppm) compared to 2. This result indicated that the addition of methoxyl and bromoalkyl group can improve the activity of the compound as a drug candidate.