Chemometric evaluation of the anti-cancer pro-drug podophyllotoxin and potential therapeutic analogues in Juniperus and Podophyllum species.
BACKGROUND
Podophyllotoxin, deoxypodophyllotoxin, demethylpodophyllotoxin and podophyllotoxone are four therapeutically potent secondary metabolites. There is a dearth of information on the holistic analysis of their distribution pattern in both phylogenetic and ecological contexts.


OBJECTIVE
To analyse the continuum of the above metabolites in Juniperus and Podophyllum species collected from natural populations in Himalayan environments and the botanical gardens of Rombergpark and Haltern (Germany) using multi-component LC-ESI-MS/MS, coupled with statistically relevant chemometric assessment.


METHODS
We evaluated the individual and holistic metabolite profiles and chemometrically correlated the phytochemical loads between various species (infraspecific), organic and aqueous extracts, and populations of the same species from different locations, different species from same location, different species from different locations and infrageneric populations from same and different locations.


RESULTS
Multivariate analysis revealed Juniperus x-media Pfitzeriana as a suitable alternative to Podophyllum hexandrum for commercial exploitation. A significant positive correlation of podophyllotoxone with both podophyllotoxin and demethylpodophyllotoxin, and a negative correlation of podophyllotoxin with both deoxypodophyllotoxin and demethylpodophyllotoxin (infraspecific among Podophyllum), were observed by Kruskal's multidimensional scaling and corroborated by principal component analysis, indicating probable similarity and/or difference between the biosynthetic pathways, and synergistic and/or antagonistic principles, respectively. Finally, linear discriminant analysis and hierarchical agglomerative cluster analysis revealed considerable infrageneric and infraspecific variability in secondary compound spectra and load of the different populations under study.


CONCLUSIONS
Such holistic studies of plants and their therapeutic metabolites ought to assist in selecting plants, geographical areas and environmental conditions for bioprospecting and global-scale phytochemical and phylogenetic diversity studies in the future.
Institut für Umweltforschung (INFU), Technische Universität Dortmund, Otto-Hahn-Strasse 6, D-44221 Dortmund, Germany.
Souvik
S
Kusari
Sebastian
S
Zühlke
Michael
M
Spiteller
D000972:Antineoplastic Agents, Phytogenic / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D016000:Cluster Analysis; D016002:Discriminant Analysis; D005858:Germany; D018653:Juniperus / Q000737:chemistry*; D015999:Multivariate Analysis; D011034:Podophyllotoxin / Q000032:analysis* / Q000737:chemistry; D011035:Podophyllum / Q000737:chemistry*; D025341:Principal Component Analysis; D011355:Prodrugs / Q000032:analysis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry
D000972:Antineoplastic Agents, Phytogenic; D011355:Prodrugs; D011034:Podophyllotoxin