New indolizidine- and pyrrolidine-type alkaloids with anti-angiogenic activities from Anisodus tanguticus

Abstract

Eleven alkaloids, including five previously undescribed indolizidine alkaloids (1, 2a, 2b, 3a, and 3b) and four new pyrrolidine alkaloids (5−8), were isolated from the roots of Anisodus tanguticus. Of these, two new pairs of enantiomeric alkaloids (2a/2b and 3a/3b) are the first examples of alkaloids containing both indolizidine and pyrrolidine structural fragments. The one-carbon bridge connections with two pyrrolidine rings (6) or with a pyrrolidine ring and a pyridine ring (8) are the first reported from nature. Extensive spectroscopic techniques were used to elucidate their structures, and NMR and ECD calculations were used to determine the absolute configurations. The viability of human umbilical vein endothelial cells (HUVECs) was inhibited by compounds 2a, 2b, 3a, 4b, and 5, and compound 2b exhibited a potential anti-angiogenic effect by inhibiting the proliferation, migration, and tube formation of HUVECs. A chorioallantoic membrane assay also demonstrated the anti-angiogenic activity of 2b. In addition, compounds 2a, 2b, 3a, and 4b exhibited moderate cytotoxicity against A2780 cells.