Ungeremine is a betaine-type alkaloid that has been found inC. zeylanicumand has diverse biological activities.^1,2,3,4It is an inhibitor of acetylcholinesterase (AChE; IC₅₀= 0.35 µM).²Ungeremine acts as a topoisomerase poison, inducing double-strand breaks in DNA by stabilizing the linkage between topoisomerase IIβ and DNA.³It inhibits the relaxation of supercoiled DNA by human topoisomerase I and -IIα andE. colitopoisomerase I and -IV (IC₅₀s = 6.1, 25.8, 15, and 7.3 µM, respectively).⁴Ungeremine 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

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 autophagyPhytomedicine60152832(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 systemBiol. 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 cellsBr. J. Cancer85(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 topoisomerasesBioorg. Med. Chem. Lett.21(23)7041-7044(2011)