Globoidnan A, rabdosiin and globoidnan B as new phenolic markers in European‐sourced comfrey (Symphytum officinale L.) root samples

Introduction: Symphytum officinale L. (comfrey, Boraginaceae) is a cultivated or spontaneously growing medicinal plant that is traditionally used for the treatment of bone fractures, hematomas, muscle pains and joint pains. A wide range of topical preparations and dried roots for ex tempore applications are marketed in European drug stores or pharmacies. Objective: The aim of this study was to perform the qualitative and quantitative analysis of pyrrolizidine alkaloids (PAs) and phenolic compounds in the hydroethanolic extracts of 16 commercial comfrey root batches purchased from 12 different European countries. Methods: Liquid chromatography hyphenated with high-resolution tandem mass spectrometry (LC-HRMS/MS) was used for the profiling of PAs and phenolic compounds, whereas LC-MS/MS and liquid chromatography with diode array detection (LC-DAD) were used for their quantification. Results: 20 PAs (i.e. intermedine, lycopsamine, acetylintermedine, acetyllycopsamine, symphytine, symphytine-N-oxide), 17 phenolic compounds (i.e. caffeic and rosmarinic acids, rabdosiin, globoidnan A, globoidnan B) and 9 nonphenolic compounds (sugars, organic and fatty acids) were fully or partly annotated in the analysed samples. In addition, the quantitative analyses revealed that globoidnan B, rabdosiin and globoidnan A are new phenolic markers that can be used together with rosmarinic acid and PAs for the quality control of commercial comfrey root batches. Conclusions: This study brings new insights into the phytochemical complexity of S. officinale, revealing not only numerous toxic PAs, but also a significant number of valuable phenolic compounds that could contribute to the bioactivities of comfreybased preparation

How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?

Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds

Echinosulfonic acids A-C and echinosulfone A: Novel bromoindole sulfonic acids and a sulfone from a southern Australian marine sponge, Echinodictyum

The crude EtOH extract of an Echinodictyum sp. collected during trawling operations in the Great Australian Eight, Australia, displayed antibacterial and antiparasitic properties. Bioassay-directed fractionation yielded three novel sulfonic acids, the echinosulfonic acids A to C (1-3), and a new sulfone, echinosulfone A (4). Structures were assigned to these compounds on the basis of detailed spectroscopic analysis. It was determined that echinosulfonic acids A-C (1-3) and echinosulfone A(4) contributed to the antibacterial but not antiparasitic activity of the crude extract

Nuapapuin A and sigmosceptrellins D and E: New norterpene cyclic peroxides from a southern Australian marine sponge, Sigmosceptrella sp.

A Sigmosceptrella sp. from the Great Australian Eight, Australia, has yielded the new norditerpene cyclic peroxide, nuapapuin A (2a), and the norsesterterpene cyclic peroxide sigmosceptrellin D (3a), characterized as the corresponding methyl esters 2b and 3b. The crude methylated sponge extract also yielded the new norsesterterpene cyclic peroxide sigmosceptrellin E methyl ester (4). Relative stereochemistry about C2, C3, and C6 was assigned by established empirical rules and absolute stereochemistry by the advanced Mosher procedure. A plausible biosynthetic pathway has been proposed that rationalizes key transformations in the biosynthesis of all known norterpene cyclic peroxides and related norterpene ketones, dienes and sigmosceptrins

Trunculins G-I: New norsesterterpene cyclic peroxides from a southern Australian marine sponge, Latrunculia sp.

A Latrunculia sp, collected off Port Phillip Bay, Victoria, returned three new norsesterterpene cyclic peroxides. Trunculins G (9), H (10) and I (11) were isolated as their methyl esters (12), (13) and (14) respectively. Gross structures for these new trunculins were assigned on the basis of spectroscopic analysis, while the absolute stereochemistry about the cyclic peroxide terminus was established by application of the Horeau and Mosher procedures

cis-3-hydroxy-N-methyl-L-proline: a new amino acid from a southern Australian marine sponge, Dendrilla sp.

A specimen of the sponge Dendrilla sp. collected during commercial trawling operations in the Great Australian Eight, Australia, analyses for a very high natural abundance of the new amino acid cis-3-hydroxy-N-methyl-L-proline (1). The complete stereostructure for (1) was determined by spectroscopic analysis and chemical derivatization

Mycaperoxides F and G and a related norterpene ketone from southern Australian marine sponges, Mycale species

Investigation of two southern Australian marine sponges, Mycale spp., resulted in isolation of the known norsesterterpene mycaperoxide F methyl ester (5) together with a new norsesterterpene mycaperoxide G methyl ester (10) and a new norterpene ketone 11. All structures were secured by spectroscopic analysis and chemical derivatization. The absolute stereochemistry previously assigned to 5 by application of the Horeau procedure has been revised by application of the Mosher procedure

Amphilactams A-D: Novel nematocides from southern Australian marine sponges of the genus Amphimedon

Bioassay-directed fractionation of the ethanol extracts of two Amphimedon spp. collected during trawling operations in the Great Australian Eight yielded four new macrocyclic lactone/lactams, amphilactams A-D (1-4). The amphilactams possess potent in vitro nematocidal properties, and their structures were assigned on the basis of detailed spectroscopic analysis and comparison with synthetic model compounds. The amphilactams feature both carbon skeletons and an enamino lactone/lactam moiety unprecedented in the natural products literature

Spermine alkaloids from Albizia adinocephala with activity against Plasmodium falciparum plasmepsin II

Crude MeOH extracts from the stem bark and leaves of a Panamanian specimen of Albizia adinocephala (Leguminosae) were found to inhibit the malarial enzyme plasmepsin II. Bioassay guided fractionation led to the isolation of two new bioactive spermine alkaloids, budmunchiamines L4 and L5. (C) 2002 Elsevier Science Ltd. All rights reserved