Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a “screening hit” through a “drug lead” to a “marketed drug” is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis.While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

Graphical abstract

A dichloromethane extract of root celery yielded falcarinol, falcarindiol, panaxydiol, and the new polyacetylene 8-O-methylfalcarindiol. The structure of the new compound was established by one- and two-dimensional (1D and 2D) NMR, mass spectrometry, and optical rotation data. Nonpolar extracts of roots and bulbs of carrots, celery, fennel, parsley, and parsnip were investigated for their content of polyacetylenes by high-performance liquid chromatography with diode array detection (HPLC-DAD). All five species contained polyacetylenes, although carrots and fennel only in minor amounts. Additionally, the cytotoxicity of the four polyacetylenes against five different cell lines was evaluated by the annexin V-PI assay. Falcarinol proved to be the most active compound with a pronounced toxicity against acute lymphoblastic leukemia cell line CEM-C7H2, with an IC(50) of 3.5 micromol/L. The possible chemopreventive impact of the presented findings is discussed briefly.

Mesotaenium berggrenii is one of few autotrophs that thrive on bare glacier surfaces in alpine and polar regions. This extremophilic alga produces high amounts of a brownish vacuolar pigment, whose chemical constitution and ecological function is largely unknown until now. Field material was harvested to isolate and characterize this pigment. Its tannin nature was determined by photometric methods, and the structure determination was carried out by means of HPLC-MS and 1D- and 2D-NMR spectroscopy. The main constituent turned out to be purpurogallin carboxylic acid-6-O-β-d-glucopyranoside. This is the first report of such a phenolic compound in this group of algae. Because of its broad absorption capacities of harmful UV and excessive VIS radiation, this secondary metabolite seems to play an important role for the survival of this alga at exposed sites. Attributes and abundances of the purpurogallins found in M. berggrenii strongly suggest that they are of principal ecophysiological relevance like analogous protective pigments of other extremophilic microorganisms. To prove that M. berggrenii is a true psychrophile, photosynthesis measurements at ambient conditions were carried out. Sequencing of the 18S rRNA gene of this alpine species and of its arctic relative, the filamentous Ancylonema nordenskiöldii, underlined their distinct taxonomic position within the Zygnematophyceae.