Trimeric and dimeric Aspidosperma-type alkaloids from leaves of Tabernaemontana divaricata 'Dwaft'

Continued interest in bioactive monoterpenoid indole alkaloids and the purpose to explore the artificial cultivation influence on the chemical composition in the same plant species, 8 undescribed Aspidosperma-type alkaloids including two unprecedented trimers, taberdivarines A-B (1-2), and six new dimers, taberdivarines C-H (3-8), together with 9 known bisindoles were isolated from the leaves of Tabernaemontana divaricata 'Dwaft'. Notably, taberdivarines A and B were the first cases of Aspidosperma-Aspidosperma-Aspidosperma-type alkaloids with furan ring linkage patterns of the natural products. Their structures were elucidated by comprehensive spectroscopic analyse. Compounds 1-8 were screened for the cytotoxicity against three human cancer cell lines, SMMC-7721, HT-29 and A549. Among them, Compound 6 exhibited significant activity against three cell lines with IC50 values of 0.30, 0.75 and 3.41 mu M, respectively (IC50 = 3.02, 0.14 and 2.23 mu M for the positive control, vinorelbine). Compound 1, 3, 4, 6, 7 and 8 also expressed varying degrees of activity. The structure-activity relationships (SARs) of these alkaloids were discussed.

Automated summary

The study explored the influence of artificial cultivation on the chemical composition of the same plant species, leading to the discovery of several undescribed bioactive alkaloids in the leaves of Tabernaemontana divaricata 'Dwaft'. Among the isolated alkaloids, taberdivarines A and B were particularly noteworthy for their unique structure. Compound 6 showed significant cytotoxic activity against three human cancer cell lines, indicating its potential as a lead compound for further research.