Preparation of Lignin-like Polymers by Dehydrogenation of Lignin Precursors and Structure-activity Relationships of the Resulting Polymers against Live Cancer HepG2 Cells

Abstract

Lignin can be used as a natural anticancer drug because of its potential biological activity and low cytotoxicity. This research focuses on oligomeric dehydrogenation polymers (DHPs) of lignin. The lignin precursor coniferin was used to yield Zulaufverfahren dehydrogenation polymers (ZL-DHPs) and Zutropfverfahren dehydropolymers (ZT-DHPs) catalyzed by mixed enzymes. The ¹³C-NMR determination showed that the DHPs obtained were similar to natural lignin, and ZL-DHP had a slightly higher β-5 content than ZT-DHP. ZL-DHPs and ZT-DHPs were subjected to organic solvent extraction with different polarities to obtain eight fractions, i.e., ZL-1-ZL-4 and ZT-1-ZT-4. The antitumor activity showed ZL-2 (IC₅₀ 181.99 μg/mL) and ZT-2 (IC₅₀ 246.76 μg/mL) had significant inhibitory effects. Fractions ZL-2 and ZT-2 were purified through column chromatography using gradient-polarity binary eluent, and 12 purified compounds were obtained, i.e., L1–L6 and T1–T6. The results showed L2 (IC₅₀ 33.99 μg/mL) and T1 (IC₅₀ 42.08 μg/mL) had relatively high biological activity, respectively. Their structure was characterized using high-resolution mass spectrometry and ¹³C-NMR, indicating that L2 is a dimer with β-5 linkage (β-5, γ-CH₃, and γ'-CH₂OH), and T1 is also a dimer with β-5 linkage but different substituents (β-5, γ-CHO, and γ'-COOH).