Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed.

The structures, origins, biogenesis, synthesis and bioactivity of a selection of N-heterocyclic marine alkaloids are reviewed. The emphasis is on compounds poised as potential anticancer drugs: lamellarins (pyrroles), cephalostatins/ritterazines (pyrazines) and ecteinascidins (isoquinolines). Also discussed are examples of bioactive marine alkaloids that have emerged as novel leads. These include manzamines (β-carbolines), variolins (pyridopyrrolopyrimidines) and the pyrroloquinoline family. This review emphasises the role of marine alkaloids as an important source of leads for drug discovery.

Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B–E (1–4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL⁻¹), the neuritogenic activity was comparable to that of the positive control (50 ng mL⁻¹ of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.

A specimen of Dendrilla cactos collected during trawling operations in Bass Strait, Australia, has yielded two new alkaloids, lamellarin-O (17) and lamellarin-P (18). Both these metabolites are examples of the lamellarin structure class, previously reported from tunicates and a mollusc; however, in these examples the pyrrole ring system is not fused to adjacent aromatic rings. The structures of (17) and (18) were secured by spectroscopic analysis and partial synthesis.