Anti-proliferative aporphine alkaloids from Litsea glutinosa and ethnopharmacological relevance to Kuuku I’yu traditional medicine

Australian Aboriginal people have a long history of relying on plants for the treatment of various ailments and illnesses. Our ongoing collaborative research project initiated by Chuulangun Aboriginal Corporation (Cape York, Australia) has recently focussed on revealing whether Kuuku I'yu plant medicines possess anticancer-related activities and the chemistry responsible for this. Here, we present results from a study of the plant Litsea glutinosa, used traditionally for the treatment of gastrointestinal disorders. Four known aporphine alkaloids N-methylactinodaphnine (1), boldine (2), N-methyllaurotetanine (3), and isoboldine (4) were isolated by activity-guided fractionation and tested for cytotoxicity against HT29, SKMEL28, and primary human keratinocytes. Compound 1 was the most cytotoxic and this observation may be explained by the presence of a 1,2-methylenedioxy group. In silico docking revealed that a plausible mechanism for the observed cytotoxicity is the stabilization of a topoisomerase II (β) DNA-enzyme complex. The ethnopharmacological relevance of this study is discussed in the context of researching and using traditional knowledge in biomolecular discovery.