Bioactive withanolides from the leaves of Athenaea velutina (Sendtn.) D'Arcy

Withanolides are a substantial bio-diverse group of naturally occurring steroidal lactones. Herein, ten still undescribed withanolides (1-10), along with the knowns withaferin A (11), 2,3-dihidrowithaferin A (12), and two other non-withanolides, vomifoliol (13) and the N-trans-p-coumaroyltyramine (14), were isolated from the hexane/EtOAc 1:1 leaf extract of Athenaea velutina (Sendtn.) D'Arcy (Solanaceae). The structures of the undescribed withanolides were elucidated by an extensive analysis of their spectroscopic data: 1D and 2D NMR, HRESIMS, single-crystal X-ray diffraction, and ECD calculations. The antiproliferative properties of the withanolides were evaluated against the human cancer cell lines: central nervous system (SNB-19), prostate (PC-3), colon (HCT-116), and leukemia (HL-60), and a murine fibroblast-like cell (L-929). Withanolides 15-17, isolated from the same plant in a previous work, were included for the pharmacological tests. Compounds 15 and 16 exhibited cytotoxic activity for all cancer cells, while 2 was selectively more cytotoxic to HL-60 cells. In addition, the withanolides were evaluated in guinea pig cardiac tissues. Compounds 15 and 16 showed cardiotonic activity, devoid of a positive chronotropic effect which is a good pharmacological profile for an inotrope agent.