Three new cardiac glycosides obtained from the roots of Streblus asper Lour. and their cytotoxic and melanogenesis-inhibitory activities

Abstract

Three new cardiac glycosides strophanthidin-3-O-α-L-rhamnopyranosyl-(1→4)-6-deoxy-β-D-allopyranoside (1), 5βH-16β-acetylkamaloside (2), and mansonin-19-carboxylic acid (3) along with seven known steroids including five cardiac glycosides were isolated from the methanol extracts of Streblus asper Lour. roots. The structures of these compounds were established by spectroscopic analyses. The cytotoxicities of crude extracts and all the isolated compounds were evaluated against four human cancer cell lines (HL60, A549, AZ521, and SKBR3). Furthermore, the selective index (SI) of each compound was measured by the ratio of cytotoxic effect on a normal cell line (WI38) to the cytotoxic effect on cancer cell line (A549). The results suggested that cardiac glycosides (2, 4, and 6–8) exhibited significant cytotoxicities with IC₅₀ values from 0.01 to 3.77 μM as well as high selective index for WI38/A549 (SI 1.50–24.26), and they displayed superior selectivities when compared with the reference cisplatin (SI 1.09). Preliminary structure–activity relationships (SARs) were also discussed regarding the type of C-10 group in the cardiac glycosides being a crucial factor in determining the cytotoxic activities and regarding the sugar moieties having much less of an active role than the type of C-10 group. In addition, the melanogenesis-inhibitory abilities of these compounds were also evaluated. Cardiac glycosides (3 and 6–8) displayed moderate inhibition effects on melanogenesis with melanin content (MC) of 26.22–74.90% at a concentration of 100 μM, thus showing high cell viability (CV: 77.94–111.70%) compared with that of the reference arbutin (MC: 82.50% and CV: 107.60%). Furthermore, western blot analysis of melanogenesis-related proteins suggested that 3 could inhibit melanogenesis by suppressing the protein expressions of TRP-2 and tyrosinase.