Semi-synthetic studies of α-onocerin derivatives for cytotoxicity

Up to 0.064% of alpha-onocerin (1) was isolated from Lycopodium clavatum. Twenty-one of its derivatives, 18 being new, were semi-synthesized through acylation, reduction, oxidation, and various other reactions. Their molecular structures were confirmed by means of NMR spectroscopy and mass spectrometry. The derivatives were evaluated for their inhibitory activities against acetylcholinesterase (AChE) and four cancer cell lines: HuCCA-1 (human cholangiocarcinoma), A-549 (lung carcinoma), HepG2 (hepatocarcinoma), and MOLT-3 (acute lymphoblastic leukemia). Introduction of a hydroxyl group at C-2/C-20 on alpha-onocerin (1) enhanced the cytotoxic activity. Most notably, the alpha-onocerin oxime derivative (22) selectively and significantly exerted cytotoxic activity against only the HepG2 cancer cell line.