Monoterpenoid indole alkaloids from Alstonia rupestris with cytotoxic, anti-inflammatory and antifungal activities

Abstract

Phytochemical investigation of the 70% EtOH extract of the leaves of Alstonia scholaris afforded seven new monoterpenoid indole alkaloids: scholarisins I-VII (1-7), and three known compounds: (3R,5S,7R,15R,16R,19E)-scholarisine F (8), 3-epi-dihydro- corymine (9), and (E)-16-formyl-5α-methoxystrictamine (10). Structural elucidation of all the compounds was accomplished by spectral methods such as 1D- and 2D-NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxicity against seven tumor cell lines, anti-inflammatory activities against Cox-1 and Cox-2, and antifungal potential against five species of fungi. Compounds 1, 6, and 10 exhibited significant cytotoxicities against all the tested tumor cell lines with IC₅₀ values of less than 30 μM and selective inhibition of Cox-2 comparable with the standard drug NS-398 (>90%). Additionally, 1, 2, 3 and 8 showed antifungal activity against two fungal strains (G. pulicaris and C. nicotianae).

Figure 1

The structures of compounds 1–10.

Figure 2

Key HMBC () and NOESY () correlations of of compound 1.

Figure 3

Key HMBC () and NOESY () correlations of of compound 4.

Figure 4

Key HMBC () and NOESY () correlations of of compound 6.

Figure 5

Key HMBC () and NOESY () correlations of of compound 7.