Mini Reviews in Medicinal Chemistry - Volume 17, Issue 12, 2017

Background: Terpenoids are hydrocarbon compounds derived from common five-carbon isoprene (C5H8) building blocks. They are formed through the condensation and subsequent modification of isoprene units in various ways including 128;“ among others 128;“ cyclization and/or oxygenation. Their synthesis is localized either to the chloroplast and/or to the cytoplasm/peroxisome/endoplasmic reticulum and mitochondrion. Terpenoids represent a very large and diverse class of metabolites and play important roles in plant growth and development. In addition, they have been intensively used in human health care, disease treatment and in dietary supplements. Approximately 60% of natural products known so far are terpenoids. Results and Discussion: This review briefly summarizes the biosynthetic pathways of major plant terpenoids. Then, five well-known and medicinally important diterpenoids, including paclitaxel, tanshinone, ginkgolide, triptolide and oridonin are discussed in detail. Their structures, occurrence, extraction and identification methods, pharmacological properties and clinical uses are also reviewed. Finally, the prospects of using biotechnology to produce medicinally important terpenoids are also briefly discussed.

Background: Plants produce a vast variety of specialized metabolites which can be a rich source for lead compounds for the development of new drugs. Alkaloids are one the largest groups of plant specialized metabolites important for natural product based pharmaceuticals. Of these, lysine (Lys)-derived alkaloids exhibit a wide range of pharmacological properties which are beneficial for humans. For instance they have anticancer, anti-Alzheimer’s disease, anti-inflammatory, hypocholesterolemic and antiarrhtymic effects. Lys-derived alkaloids are widely distributed throughout the plant kingdom: they can be found in various species from clubmosses to flowering plants. Lys is one of the most essential amino acids for humans and livestock and is synthesized in the plastids of land plants. Lys-derived alkaloids can be divided into four major groups including quinolizidine, lycopodium, piperidine, and indolizidine alkaloids. Despite the importance of these compounds, the biosynthetic pathways of Lys-derived alkaloids are not well understood. With the exception of indolizidine alkaloids, Lys decarboxylase (LDC) is the enzyme involved in the first committed step of the biosynthesis by catalyzing the transformation of L-Lys into cadaverine. Cadaverine is then oxidized by copper amine oxidase (CuAO) and spontaneously cyclized to Δ1-piperideine Schiff base which is a universal intermediate for the production of various Lys-derived alkaloids. Conclusion: In this review, we briefly summarize the recent understanding about the structures, occurrences, analytical procedures, biosyntheses, and potential health effects and medical applications of Lys-derived alkaloids with emphasis on quinolizidine alkaloids (QAs).

Objective: There has been a massive increase in the number of reports about the medicinal benefits of the consumption of phenylpropanoids derived from the plastidic shikimate pathway. These benefits include anti-retroviral, anti-hypertensive, anti-inflammatory, anti-aging and insulin-sensitizing activities, the reduction of the risk of a range of chronic diseases including cardiovascular disease, cancer and osteoporosis as well as inhibition of LDL (low-density lipoprotein) oxidation. In addition, chorismate-derived salicylate which was originally isolated from plants, albeit now under chemical production, is massively used for pain relief in the form of acetylsalycilic acid, namely aspirin. Chorismate also acts as precursor in the biosynthesis of folate and phylloquinone, i.e., vitamins B9 and K1, respectively. Results: Cumulative evidence suggests that deficiencies of either of these vitamins in the diet can result in a wide range of diseases. In parallel to our enhanced comprehension of the dietary importance of shikimate-derived compounds, the advent of metabolomics and the development of next-generation sequencing technologies have dramatically accelerated advances in our understanding of the biosynthetic, decorative and degradation pathways underlying their metabolism. Furthermore, forward and reverse genetic approaches have begun to facilitate the metabolic engineering of plants for biofortification of these compounds. Conclusion: Here we review data about the bioactivities of these compounds and provide an overview of our current understanding of biosynthesis, molecular function and their in planta occurrence. Finally we discuss the future perspectives and the importance of further development of cross-disciplinary research efforts in this rapidly expanding research field.

Background: Phylloquinone is a prenylated naphthoquinone that is synthesized exclusively by plants, green algae, and some species of cyanobacteria, where it serves as a vital electron carrier in photosystem I and as an electron acceptor for the formation of protein disulfide bonds. In humans and other vertebrates, phylloquinone plays the role of a vitamin (vitamin K1) that is required for blood coagulation and bone and vascular metabolism. Phylloquinone from green leafy vegetables and vegetable oil represents the major dietary source of vitamin K for humans. In recent years, reverse genetics and biochemical approaches using the model plant Arabidopsis thaliana have shown that phylloquinone biosynthesis in plants involves paralogous and multifunctional enzymes, a compartmentation of the corresponding pathway in plastids and peroxisomes, and trafficking of some biosynthetic intermediates within plastids themselves. Furthermore, phylloquinone biosynthetic intermediates create crucial metabolic branch-points with other plastid-synthesized metabolites such as chlorophylls, tocopherols and salicylate. This review presents an update on recent studies of the central role of plastids in the biosynthesis of phylloquinone, in particular on the discovery of novel enzymatic steps that are likely paradigms for phylloquinone and menaquinone (vitamin K2)-synthesizing organisms alike.

Objective: This review examines various aspects of vitamin E, both in plant metabolism and with regard to its importance for human health. Vitamin E is the collective name of a group of lipidsoluble compounds, chromanols, which are widely distributed in the plant kingdom. Their biosynthetic pathway, intracellular distribution and antioxidant function in plants are well recognized, although their other functions are also considered. Conclusion: Analytical methods for the determination of vitamin E are discussed in detail. Furthermore, the vitamin E metabolism and its antioxidant action in humans are described. Other nonantioxidant functions of vitamin E are also presented, such as its anti-inflammatory effects, role in the prevention of cardiovascular diseases and cancer, as well as its protective functions against neurodegenerative and other diseases.

Objective: Dibenzylbutyrolactone lignans represent a unique group of plant secondary metabolites with increasing significance in medicine. This review summarizes their structural characteristics and classification, as well as the biosynthesis starting in the chloroplast, and their supposed biological activity associated with plant defense mechanisms are also discussed. Over 85 natural dibenzylbutyrolactone lignans known to date and their corresponding plant sources are summarized herein for the first time, highlighting a taxon- and organ-specific accumulation of these compounds. Conclusion: The isolation strategies, applied analytical methods and pharmacological activities of dibenzylbutyrolactone lignans are also thoroughly reviewed.

Background: Vitamins are chemical compounds whose derivatives are involved in vital metabolic pathways of all living organisms. The complete endogenous biosynthesis of vitamins can be performed by many bacteria, yeast and plants, but humans need to acquire most of these essential nutrients with food. In recent years, new types of action of the well-recognized vitamins or their more sophisticated relationships have been reported. Objectives: In this review we present the current knowledge of factors that can influence the yield and regulation of vitamin B1), B2), B3) and B9) biosynthesis in plants which can be important for human nutrition. A summary of modern methods applied for vitamin analysis in biological materials is also provided. Contributions of selected vitamins to the homeostasis of the human organism, as well as their relations to the progress or prevention of some important diseases such as cancer, cardiovascular diseases, diabetes and Alzheimer's disease are discussed in the light of recent investigations. Better understanding of the mechanisms of vitamin uptake by human tissues and possible metabolic or genetic backgrounds of vitamin deficiencies can open new perspectives on the medical strategies and biotechnological processes of food fortification.

Background: The fatty acids of seed plants and microalgae stored in triglyceride are all produced in the plastid and incorporated into triglycerides by a complex biochemical exchange between the plastid envelope and the endoplasmic reticulum. The oils of seed plants provide the basis for vegetal fat production and the microalgal fats represent an important part of the basal food web of the marine environment. The health-promoting properties of these various sources of fats and in particular the long-chain polyunsaturated fatty acids of marine microalgae are widely recognized. The omega-3 fatty acids are known to have benefits on health and disease. Indeed, alpha-linolenic, eicosapentaenoic (EPA) and docosahexaenoic acids (DHA) are linked to the regulation of mechanisms involved in numerous biological functions associated with cardiovascular disease and cancer prevention. Most EPA and DHA sources for human nutrition are provided by decreasing global stocks of fish. This is one of the reasons why industrial research has been directed towards more sustainable sources of these “marine” lipids. The synthesis of fatty acids and triglycerides are in many respects similar in higher plants and marine algae, but there are also important differences. Conclusion: This mini-review covers the biochemistry of fatty acid and lipid synthesis in marine microalgae, and the potential health impact of the different fats is also discussed.