Terpenes, also known as terpenoids or isoprenoids, constitute the structurally most diverse family of natural products and comprise over 80,000 compounds produced by diverse organisms such as plants, fungi, insects, marine organisms and animals. In plants, they function as important mediators of antagonistic and mutualistic ecological interactions. They are also involved in cell growth modulation, plant elongation, light harvesting and photoprotection.
All terpenes originate from only two isomeric C5 precursor molecules that biosynthetically interconvert into each other by their corresponding isomerases: the electrophilic dimethylallyl diphosphate (DMAPP) and the nucleophilic isopentenyl diphosphate (IPP). Successive elongation reactions from DMAPP and IPP, more often bond to each other by head-tail linkages, lead to geranyl diphosphate (GPP, C10), farnesyl diphosphate (FPP, C15), geranylgeranyl diphosphate (GGPP, C20), and geranylfarnesyl diphosphate (GFPP, C25) structures. In turn, these elongated molecules are cyclized to generate respectively the monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20) and sesterterpenes (C25). Alternatively, the fusion and subsequent reactions of two FPP (C15) or two GGPP (C20) moieties affords triterpenes (C30) or tetraterpenes (C40). Finally, the cyclization and subsequent biosynthetic steps of the triterpene squalene affords lanosterol and cycloartenol, which are precursors of a wide spectrum of steroids responsible for membrane fluidity and signal transduction, among other important cellular functions in living organisms.
Of all drugs currently available on the market, more than 66% are derived or inspired from natural products and biological macromolecules. Within this scenario, terpenes have led to the development of important drugs over the last century. For instance, Taxol®, an anticancer drug, artemisinin, an antimalarial drug, and cannabidiol, an anti-epileptic drug, are only a few examples of types of drugs developed from terpenes.
Undoubtedly, the use of bioactive terpenes as chemical scaffolds for novel compounds with improved drug-likeness, pharmacokinetic and pharmacodynamic properties is a promising strategy for the success of a drug discovery campaign. Valid approaches for this purpose may include semisynthesis of analogues from isolated terpenes, the total synthesis of terpene derivatives which may involve bioisosterism and/or molecular simplification, or even the synthesis of a larger set of analogues that will be useful for investigation of structure–activity relationships (SAR) within the rational drug design process.
This Research Topic aims to invite submissions of the most recent research progress associated with bioactive terpenoids as inspiring molecules for the development of novel drug candidates.
We encourage submissions of original research articles, perspectives, opinion articles, and reviews from all over the world that might include, but are not limited to, the following topics:
- Isolation and characterization of novel naturally occurring terpenoids and/or derivatives with remarkable pharmacological effects;
- Assessments of the pharmacological activity of terpene enriched extracts and herbal mixtures, provided that their chemical profile is included following the ConPhyMP statement (see below);
- Prediction of potential molecular targets of terpenoids and their mechanisms of action using in silico approaches if these are combined with an in vitro or in vivo evaluation;
- Structure–activity relationship (SAR) studies on terpenoids and analogues;
- Innovative drug development involving novel lead compounds and drug candidates inspired in bioactive terpenoids.
All manuscripts dealing with extracts must comply with guidelines of the section Ethnopharmacology - the four pillars of best practice in ethnopharmacology (see
here for further information ) Specifically, please note the need to phytochemically characterise the preparations used in detail ( see
here for further information ). In silico studies of plants/fungi and their extracts are outside of the journals scope.