A new C–C linked benzophenathridine–2-quinoline dimer, and the antiplasmodial activity of alkaloids from Zanthoxylum holstzianum

Abstract

The CH₂Cl₂/MeOH (1:1) extract of Zanthoxylum holstzianum stem bark showed good antiplasmodial activity (IC₅₀ 2.5 ± 0.3 and 2.6 ± 0.3 µg/mL against the W2 and D6 strains of Plasmodium falciparum, respectively). From the extract five benzophenanthridine alkaloids [8-acetonyldihydrochelerythrine (1), nitidine (2), dihydrochelerythine (3), norchelerythrine (5), arnottianamide (8)]; a 2-quinolone alkaloid [N-methylflindersine (4)]; a lignan [4,4′-dihydroxy-3,3′-dimethoxylignan-9,9′-diyl diacetate (7)] and a dimer of a benzophenanthridine and 2-quinoline [holstzianoquinoline (6)] were isolated. The CH₂Cl₂/MeOH (1:1) extract of the root bark afforded 1, 3–6, 8, chelerythridimerine (9) and 9-demethyloxychelerythrine (10). Holstzianoquinoline (6) is new, and is the second dimer linked by a C-C bond of a benzophenanthridine and a 2-quinoline reported thus far. The compounds were identified based on spectroscopic evidence. Amongst five compounds (1-5) tested against two strains of P. falciparum, nitidine (IC₅₀ 0.11 ± 0.01 µg/mL against W2 and D6 strains) and norchelerythrine (IC₅₀ value of 0.15 ± 0.01 µg/mL against D6 strain) were the most active.

Graphical Abstract

Keywords:

• Antiplasmodial
• benzophenanthridine alkaloid
• holstzianoquinoline
• rutaceae; Zanthoxylum holstzianum

Authors’ contributions

A.D. carried out the isolation, structural determination and writing the manuscript; A.Y. structural determination and writing the manuscript; H.M.A. carried out antiplasmodial bioassay experiments; M.H., spectroscopic analysis and structural determination; S.D., research supervision and structural determination. All authors read the manuscript.

Acknowledgements

A.D. is grateful to the German Academic Exchange Services (DAAD) for a scholarship which was awarded through the Natural Products Research Network for Eastern and Central Africa (NAPRECA). The International Science Program (ISP Sweden, grant KEN-02), and the Kenya Medical Research Institute’s Internal Research Grant L-183, are acknowledged for financial support. Mr. Patrick Mutiso for identification of the plant.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was partly supported by International Science Program (ISP Sweden, grant KEN-02), and the Kenya Medical Research Institute’s Internal Research Grant L-183.