An Overview of Biotransformation and Toxicity of Diterpenes

Abstract

Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities, and some isolated diterpenes are produced at commercial scale to be used as medicines, food additives, in the synthesis of fragrances, or in agriculture. There is great interest in developing methods to obtain derivatives of these compounds, and biotransformation processes are interesting tools for the structural modification of natural products with complex chemical structures. Biotransformation processes also have a crucial role in drug development and/or optimization. The understanding of the metabolic pathways for both phase I and II biotransformation of new drug candidates is mandatory for toxicity and efficacy evaluation and part of preclinical studies. This review presents an overview of biotransformation processes of diterpenes carried out by microorganisms, plant cell cultures, animal and human liver microsomes, and rats, chickens, and swine in vivo and highlights the main enzymatic reactions involved in these processes and the role of diterpenes that may be effectively exploited by other fields.

Diterpenes and their derivatives as promising agents against dengue virus and dengue vectors: A literature‐based review

“…Biotransformation can be a useful approach in discovering drugs and could be useful in screening drug candidates for possible transformation to active metabolites during the discovery stage. This is crucial in developing methods to obtain more efficient derivatives of therapeutically active lead compounds (Kebano, Tesema, & Geleta, 2015), including diterpenes (de Sousa et al, 2018). For examples, phytanic acid, a biotransformation product of phytol (a chlorophyllderived diterpenoid) is evident for its promising biological effects (Islam, Ali, et al, 2016b), including antimicrobial activity (Rajab, Cantrell, Franzblau, & Fischer, 1998), whereas seven metabolites of cryptotanshinone have been reported to exert significant antiinfluenza A virus activity (He et al, 2017).…”

“…Accumulated reports suggest that terpenes and their derivatives have great commercial value and have been widely used in traditional medicine in many countries in the world for the treatment of several conditions, including microbial and parasitic infections, dermatological problems, microbial resistance, and neglected diseases (Barros de Alencar et al, 2017;Orchard & van Vuuren, 2017). Diterpenes are C 20 compounds consisting of four isoprene (C 5 H 8 ) units found in plants, fungi, bacteria, and animals in both terrestrial and marine environments (de Sousa, Sousa Teixeira, & Jacometti Cardoso Furtado, 2018). The biochemically active isoprene units, isopentenyl diphosphate and dimethylallyl diphosphate, may be derived from mevalonate and deoxyxylulose phosphate pathways .…”

Biochemistry of Terpenes and Recent Advances in Plant Protection

“…Diterpenes from various sources have exhibited inhibitory effects against pathogenic microbes, herbivore pests, and weeds. These promising biological activities place them among the essential agricultural secondary metabolites with potential in the production of biopestides [ 31 ]. Rice plants produce several phytoalexins and allelochemical diterpenes for protection against pathogens, pests, and weeds.…”

Cumulative Production of Bioactive Rg3, Rg5, Rk1, and CK from Fermented Black Ginseng Using Novel Aspergillus niger KHNT-1 Strain Isolated from Korean Traditional Food

“…Due to this importance of different ginsenosides deglycosylation, compound k (CK) and Rh1 are more detected in the circulatory system [3]. To neutralize this bioconversion in human metabolism, it is essential to convert to the necessary ginsenosides before administrating to the human body [4]. Physical methods such as steaming, sulfur fumigation, and microwave treatment were adopted for this approach; however, such treatment was not found in its application in industrial commercialization, except for the steaming process.…”