Chippiine, iboga, cleavamine, vobasine, and cytotoxic bisindole alkaloids from Tabernaemontana polyneura

Abstract

Eight undescribed indole alkaloids, polyneurines I–P (1−8), comprising one chippiine, two iboga, one cleavamine, three vobasine, and one vobasinyl-iboga bisindole alkaloid, were isolated from the bark of Tabernaemontana polyneura. The structures of these undescribed alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, and TDDFT-ECD method. Polyneurines I (1) and J (2) are characterized by the presence of an additional pyrrolidine ring incorporated within the chippiine or seco-coronaridine skeletal framework. Biosynthetic pathways towards the formation of polyneurines I (1) and J (2) are proposed. Polyneurine P (8), along with four known bisindoles, showed appreciable cytotoxicity against HT-29, HCT 116, MDA-MB-231, and A549 cancer cell lines with IC50 values ranging between 0.3 and 9.0 μM. The variation in alkaloidal content observed between the present and previous study, both involving the same plant species but occurring at different locations, is also discussed.