Ungeremine

Ungeremine is a betaine-type alkaloid that has been found in C. zeylanicum and has diverse biological activities.^1,2,3,4 It is an inhibitor of acetylcholinesterase (AChE; IC₅₀ = 0.35 µM).² Ungeremine acts as a topoisomerase poison, inducing double-strand breaks in DNA by stabilizing the linkage between topoisomerase IIβ and DNA.³ It inhibits the relaxation of supercoiled DNA by human topoisomerase I and -IIα and E. coli topoisomerase I and -IV (IC₅₀s = 6.1, 25.8, 15, and 7.3 µM, respectively).⁴ Ungeremine inhibits the growth of HL-60, MOLT-4, K562, U937, and LXFL 529L cells (IC₅₀s = 1.3, 0.7, 0.8, 2.5, and 1.2 µM, respectively). It is cytotoxic to a variety of drug-sensitive and -resistant cancer cells (IC₅₀s = 4.89-6.45 and 3.67-75.24 µM, respectively) and induces ferroptosis, necroptosis, apoptosis, and autophagy in CCRF-CEM leukemia cells. Ungeremine (60 mg/kg twice per week) also reduces tumor growth in a GXF251L mouse xenograft model.³

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1. Mbaveng, A.T., Bitchagno, G.T.M., Kuete, V., et al. Cytotoxicity of ungeremine towards multi-factorial drug resistant cancer cells and induction of apoptosis, ferroptosis, necroptosis and autophagy. Phytomedicine 60, 152832 (2019).

2. Rhee, I.K., Appels, N.M.G.M., Hofte, B., et al. Isolation of the acetylcholinesterase inhibitor ungeremine from Nerine bowdenii by preparative HPLC coupled on-line to a flow assay system. Biol. Pharm. Bull. 27(11), 1804-1809 (2004).

3. Barthelmes, H.U., Niederberger, E., Roth, T., et al. Lycobetaine acts as a selective topoisomerase IIβ poison and inhibits the growth of human tumour cells. Br. J. Cancer 85(10), 1585-1591 (2001).

4. Casu, L., Cottiglia, F., Leonti, M., et al. Ungeremine effectively targets mammalian as well as bacterial type I and type II topoisomerases. Bioorg. Med. Chem. Lett. 21(23), 7041-7044 (2011).