Chemical profiling of cultivated and wild African ginger and absolute configurations of compounds from mangroves and Ancistrocladus species

Abstract

Medicinal plants and natural products have played a pivotal role as a source of drug leads that has led to improving health conditions and have provided humankind with numerous pharmacologically active drugs. Other than the biological screening and chemical profiling of plant extracts, the isolation, purification and elucidation of the full absolute structures of natural compounds are some of the key areas required in the time-consuming process of drug discovery based on natural products. Elucidation of the absolute configuration (AC) of chiral natural products represents one of the most challenging tasks in the determination of full molecular structures but still remains an essential concept in drug discovery as enantiomers do not always exhibit the same pharmacological activities. The present study successively investigated the UPLC MS and GC MS chemical profiles of organic extracts from the wild and cultivated popular, but threatened medicinal plant, African ginger {i.e., Siphonochilus aethiopicus (Schweinf.) B.L. Burtt} and the absolute configurations of limonoids, diterpenoid and dimeric naphthylisoquinoline (NIQ) alkaloids isolated from mangroves and Ancistrocladus species. The first part of the study aimed at exploring the similarities and/or differences between the UPLC MS and GC MS chemical profiles of wild and cultivated African ginger rhizomes and evaluating the antimalarial activity of extracts from both sources taking into account that traditional healers are not unanimous on using the cultivated material for medicinal purposes. UPLC MS chemical profiling of n-hexane/DCM (1:1) extracts from air-dried rhizomes has revealed the presence of additional peaks in the chromatographic profiles of wild plants but also confirmed the major peak in the profiles of both wild and cultivated rhizomes to be the common furanoterpenoid (4), known as Siphonochilone. The compound was unexpectedly observed to be highly unstable and generated artefact sesquiterpenoids after autoxidation. Autoxidation was observed for the pure compound, as well as in dried and powdered rhizomes. The latter aspect confirmed that the artefact sesquiterpenoids only form after autoxidation and do not occur in the fresh plant as reported in many publications. GC MS analyses of n-hexane extracts from fresh, air-dried and oven-dried plants confirmed the presence of Siphonochilone (4) from both sources but further revealed the presence of eucalyptol, which was significantly depleted after drying. Antimalarial screenings of n-hexane/DCM (1:1) extracts against the chloroquine-sensitive (CQS) strain of Plasmodium falciparum (NF54) did not show substantial change in the IC50 values for both sources. The second part of the study aimed at elucidating the absolute configurations of two limonoids, one diterpenoid and two NIQ dimers. This was tackled by conducting quantum-chemical calculations of chiroptical spectroscopy, such as circular dichroism. Absolute configurations were deduced from the comparison between experimental chiroptical data with the curves predicted for the possible enantiomers. The absolute configurations of the limonoids thaixylomolin A (12) and B (13) were respectively revealed as 1R,5R,8R,9R,10R,13S,14R,15S,17S and 1R,2R,3S,4R,5S,9S,10R,13R,17R while that of the diterpenoid decandrinin (14) was 5S,9S,10R and those for the NIQ dimers mbandakamines A (15a) and B (15b) validated published data.