Abstract
Triterpenoids are nature-derived compounds, broadly distributed in plant kingdom in a free form as well as in a form of numerous glycosides. The complex structures of triterpenoids chiefly involve squalene derivatives, lanostanes, cycloartanes, dammaranes, euphanes, tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleananes, friedelanes, ursanes, hopanes, serratanes and another less known groups. These compounds present interesting and perspective subject for experiments, chemical and biological as well. As it is known from literature data, triterpenoids and their saponins with respect to their multitude pharmacological activities could be involved in several areas such as chemistry, medicine and pharmacology, biomedicine and agrochemical sciences. The special structure of triterpenic skeletons allows to perform numerous chemical transformations in order to obtain many new derivatives with pharmacological activity. Taking under consideration the above data, chemistry, biology and pharmacology of triterpenoids and their saponins appear to be riped for revisiting. Therefore, this special issue aims to review the advances in triterpenoids science during the last decade. Carcinomas are probably the second leading cause of death in humans, so scientists intense their research upon the development of new biological sources with antitumor activity. Medicinal plants are now the most promising sources of new potent substances in cytotoxic drug development. As Csuk presented in his work, such compound of anticancer activity is glycyrrhetinic acid, obtained e.g. from liquorice, known as sweetwood (Glycyrrhiza glabra) and some derivatives obtained from this triterpenic acid. Antitumor activity also exhibits, as presented by Paduch and Kandefer-Szerszeń, other triterpenes, such as: asiatic acid, betulinic acid, boswellic acid, lupeol, oleanolic acid or ursolic acid and their analogs and derivatives. These compounds exhibit a cytotoxicity against a variety of tumor cell lines comparable to some clinically used drugs. Most of them also have important antiviral properties, especially anti-HIV activity, which makes them potentially useful additives to current anti-HIV therapy. Another group of triterpenoids with anticancer and antiviral activity is limonoids family, belonging to tetranortriterpenoids. As Pękala and co-workers present, limonoids are a very valuable group of triterpenoids because of a wide spectrum of biological properties, such as cytotoxic, antimalarial, anti-inflammatory, antifeedant, antiviral, neuroprotective, antimicrobial, antibacterial, antifungal and other activities. Limonoids present rich variety of structures: until 2011, about 1300 limonoids with more than 35 carbon frameworks had been isolated from four families (Meliaceae, Rutaceae, Simaroubaceae, and Cneoraceae). The unique structural features of these terpenoids have attracted continuous attention of chemists and pharmacologists. Triterpenoids often occur as ingredients of daily diet or of herbal products used for therapeutic purposes. These phytochemicals occur in nature in free form or as glycosylated compounds, known as saponins, due to their characteristic foaming properties. Pharmacological activities of saponins are very broad and include numerous directions of action which were discussed in many works. Podolak and Janeczko summarize pharmacological properties of natural, non-glycosylated triterpenoids, that were reported over the last five years. The work discusses e.g. antimicrobial, cytotoxic, anti-inflammatory, antinociceptive, antidiabetic, hepatoprotective, wound healing and other activities of triterpenoids, focusing on less known compounds. Plants remain as the most viable source of triterpenoid saponins. As plants are the source of pharmacologically active saponins and free triterpenoids, it is obvious that the development of new methodologies to improve saponin yields is a significant issue. As Yendo et al. state in their work current challenges to improve triterpenoid saponin production including a better understanding of the signal transduction pathways leading to their accumulation, isolation and heterologous expression of biosynthetic genes, as well as structural and modeling studies of biosynthetic enzymes and their catalytic mechanisms. Some triterpenoids and their semi-synthetic derivatives can be identified as potential therapeutics against neurodegenerative diseases. Ruszkowski and Bobkiewicz-Kozlowska discuss the ability of celastrol, oleanolic acid, ursolic acid, asiatic acid, erythrodiol, and some triterpenoid saponins to protect the brain against neurodegeneration and neuroinflammation processes. The authors focus on triterpenoids as possible drugs to treat or slow the progression of neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis and multiple sclerosis (MS). Further, pharmacological activities of naturally-derived triterpenenoids and some of their synthetic derivatives are discussed by Jeong and Bae, Jaworska-Paszel et al. and by Luo et al. The anti-inflammatory effect is a common property of many triterpenoids. Jeong and Bae discuss the anti-inflammatory property of several triterpenoids derived from natural sources and from chemical synthesis. These triterpenoids include avicins, boswellic acid, celastrol, diosgenin, escin, ginsenosides, glycyrrhizin, lupeol, oleanolic acid, platycodon D, saikosaponins, ursolic acid, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and some of their derivatives. Jaworska-Paszel et al. describe anti-inflammatory, antioxidative, antitumor, antileukemic, hepatoprotective, gastroprotective, cardioprotective and many other important pharmacological activities of oleanolic acid. Luo et al. focus on recent advances in enone and NOreleasing derivatives of oleanolic acid with anti-cancer activity. Other compounds exhibiting numerous pharmacological activities are betulin and betulinic acid, both with pentacyclic lupane-type skeleton. Betulin, betulinic acid and their derivatives have been studied in the last decades for their diversified pharmacological activities like anti-HIV, anticancer, antibacterial, anti-inflammatory and many others. In the last few years, great progress had been made on the synthesis and biological activity of triterpenoids derived from betulin and betulinic acid. Shi and co-workers discuss recent research and development in chemistry of betulin and betulinic acid and present recent modification within A-ring, E-ring, both, at the C-3 and at the C-28 position as well as at the C-30 position of betulin and betulinic acid. The authors also present methods of conjunction of the above triterpenes with drugs. Supercritical fluid extraction has been a widely studied green technology to obtain triterpenoids enriched extracts from various vegetable matrices. De Melo and co-workers discuss research advances regarding the supercritical fluid extraction of triterpenoids in terms of biomass sources, operating conditions and their optimization, and modeling. The authors provide overview concerning the recent works (both publications and patents) upon supercritical fluid extraction of plant material leading to triterpenoids with the most important experimental and/or theoretical information. Many families of bioactive natural products are usually extracted from numerous plant sources in low yields. Triterpenic acids belong to a group of the most often studied compounds, mainly because of their abundance in a large number of food and medicinal plants. Domingues et al. in their work present overview of the biogenetic origin of some triterpenic acids, on the analytical extraction and hyphenated methodologies (mainly GC-MS) used on their identification and quantification. The authors also present an overview of the major sources of some triterpenic acids, indicating their potential large scale production pathways, with especial emphasis on abundant agroforestry biomass residues. The future perspectives towards improved therapeutic strategies using these triterpenic acids are also discussed herein. The root bark of the Chinese medicine Tripterygium wilfordii contains a quinone methide triterpenoid - celastrol. Literature data presents, that celastrol is one of the most potent antitumor activity compounds among the natural triterpenoids. Salvador et al. discuss different mechanisms of antitumor activity of celastrol, such as abilities of inhibing proliferation, inducing apoptosis and suppressing invasion and metastasis of tumor cells. The authors also describe the anticancer property of semi-synthetic celastrol derivatives. As they noticed, the quinone methide moiety is required for its antitumor activity. I thank all the contributors or this special issue and hope that the progresses highlighted in the topics covered will inspire more research in this challenging area of organic synthesis. I thank Prof. Atta-ur-Raman for the kind invitation to be the Guest Editor of this issue and all the reviewers for their time and valuable comments. I also thank Ms. Hina Wahaj (Publications Manager, Bentham Science Publishers) for the help in organizing this issue.
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