Antileishmanial activity of bisbenzylisoquinoline alkaloids from the genus Thalictrum

As part of ongoing efforts to discover natural product compounds with antileishmanial activity as potential new drug candidates, we have recently begun screening a compound library comprising natural products and precursors in their total synthesis against Leishmania donovani promastigotes. One such sample, tb-00069, exhibited activity in this in vitro assay. The identity of tb-00069 was confirmed by NMR and MS to be N-desmethylthalrugosidine [1], a bisbenzylisoquinoline alkaloid isolated earlier from the roots of Thalictrum alpinum that has not been reported to be active against L. donovani. This work further represents the first full spectroscopic characterization of 1 as its structure was originally determined by chemical degradation techniques. Another sample, tb-00078, was shown to also be active in the same bioassay. It was suggested to have a similar structure to 1 and was examined by NMR and MS for structural verification.