Structure-based insights into novel alkylated pyrrole and flavonoid from Dracaena reflexa as potential inhibitors of SARS-CoV-2 main and spike protease with ADME analysis

基于结构的新型烷基化吡咯和黄酮类化合物从龙血树(Dracaena reflexa)中分离得到,它们作为SARS-CoV-2主蛋白酶和刺突蛋白酶的潜在抑制剂,并进行了ADME分析。

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Abstract

Dracaena reflexa is a medicinal plant traditionally used for various therapeutic purposes. This study focused on the isolation, characterization and anti-viral evaluation of bioactive constituents from its stem (dichloromethane extract) and leaves (ethanol extract). Chromatographic techniques yielded two compounds: Compound (1) is 3-(6',8'-dimethoxydodecyl)-4-(4-hydroxyphenyl)-1H-pyrrole-2,5-dione, a novel alkylated pyrrole derivative and Compound (2) is 3,3',4',5,7-pentahydroxyflavon, a flavonoid reported for the first time in Dracaena reflexa. Structural elucidation was conducted using UV-Vis, FTIR, ¹H-NMR, ¹³C-NMR and mass spectrometry. Molecular docking studies targeting SARS-CoV-2 main protease (Mpro) and spike protein (Spro) revealed that Compound (2) exhibited stronger binding affinities (- 7.92 and - 8.47 kcal/mol, respectively) compared to Compound (1) (- 4.85 and - 6.60 kcal/mol) and was comparable to the reference drug, ivermectin. In silico ADME analysis showed that both compounds conformed to Lipinski's Rule of Five and displayed favorable pharmacokinetic properties, including good solubility, lipophilicity and gastrointestinal absorption. Compound (2) also exhibited better drug-likeness and bioavailability characteristics. These findings suggest that both compounds, particularly Compound (2), hold promise as lead candidates for the development of antiviral agents against SARS-CoV-2. Further in vitro and in vivo studies are recommended to validate their therapeutic potential. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00555-1.

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