Voagafries A–E, undescribed indole alkaloids with anti-glioma activity from Voacanga africana.

Voagafries A–E, five undescribed monoterpenoid indole alkaloids (MIAs), were isolated from the stem bark of Voacanga africana. Voagafrie A (1) has a unique 6/5/5/6/6 spiral ring skeleton with an indolone-fused 9-oxo-3-aza-tricyclo[6,3,1,03,7]-12-alkane-10-carbonyllactone. Voagafrie B (2) is a rare 5,6-seco diazine scaffold, whereas voagafrie C (3) possesses an octahydropyrrolo[2,3-b] pyrrole-fused 2,8-diazabicyclo[3.3.1] nonane. In addition, voagafrie D (4) represents an additional 3C ibogamine-type MIA. Their structures were elucidated using extensive spectroscopic and computational analyses and a plausible biosynthetic pathway originating from conopharyngine was proposed. Furthermore, voagafries B (2) and E (5) exhibited significant cytotoxicity against SH-SY5Y at 10 μmol/L with cell viabilities of 72.7 ± 3.8 and 79.5 ± 2.1, respectively, which were comparable to that of the positive drug paclitaxel (64.1 ± 0.9). Based on the research on several cell death-related factors, these compounds may be involved in apoptosis; therefore, it is necessary to advance our understanding of them through future studies. Five undescribed monoterpenoid indole alkaloids Voagafries A–E (1–5) were obtained from Voacanga africana. Voagafries B and E (2 and 5) exhibited significant cytotoxicity against glioma cell SH-SY5Y. [Display omitted] • Five undescribed indole alkaloids were obtained from Voacanga africana. • Structures of five compounds were confirmed by spectroscopy and ECD analyses. • Compound 1 possesses an unprecedented 6/5/5/6/6 spiral ring skeleton. • 2 and 5 exhibited potent anti-glioma activity by regulating apoptotic pathway. [ABSTRACT FROM AUTHOR]