Special Issue "Triterpenes and Triterpenoids"

Guest Editor
Prof. Dr. Vassilios Roussis
University of Athens, School of Pharmacy, Department of Pharmacognosy and Chemistry of Natural Products, Panepistimiopolis Zografou, GR 15771, Athens, Greece
E-mail:

Natural product chemistry and medicinal chemistry of triterpenes and triterpeniods, Squalene, Material science, Biomaterials, Bioassay, Pharmacological activity, Medicinal plant, Herb, Herbal medicine, Chinese medicine, Fungus, Mushroom.

Manuscript ID: molecules-triterp-20080918-za-Dubery
Type of Paper: Review
Title: Triterpenoid acids and triterpenoid glycosides in Centella asiatica (L.)., a valuable medicinal herb
Authors: Jacinda James and Ian A Dubery
Affiliation: Department of Biochemistry, University of Johannesburg, South Africa
E-mail: idubery@uj.ac.za
Abstract: Centella asiatica and other related species accumulate large quantities of pentacyclic triterpene saponins. Centella triterpenoids include asiaticoside, centelloside, madecassoside, brahmoside, brahminoside, thankuniside, sceffoleoside, centellose, and asiatic, brahmic, centellic and madecassic acids. Triterpene saponins are common secondary metabolites and a number of these molecules are synthesized via the isoprenoid pathway to produce a hydrophobic triterpenoid structure (aglycone) containing hydrophilic sugar chain (glycone). These characteristics have been attributed to the biological activity of saponins. The Centella triterpenoids can be regarded as phytoanticipins due to their antimicrobial activities and protective role against attempted pathogen infection. Preparations of C. asiatica are used in traditional and alternative medicine due to the wide spectrum of pharmacological activities associated with these secondary metabolites. Here, the biosynthesis of triterpenoid saponins and –sapogenins is reviewed and the range of metabolites found in C. asiatica summarized, together with their known biological activities. In addition, most plant-derived pharmacologically active compounds have complex structures, making chemical synthesis an economically uncompetitive option. A particular important benefit is the ability to manipulate and improve the production of desired compounds, thus biotechnological approaches to increase the concentrations of the metabolites are discussed.

Manuscript ID: molecules-triterp-20080922-es-Martin
Type of Paper: Article
Title: Clavaric acid and fasciculic acid: Biosynthesis and Molecular Genetics
Authors: Juan F. Martín ^1,2 and Ramiro P. Godio ²
Affiliations: ¹ Área de Microbiología, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, Campus de Vegazana, s/n. 24071 León, Spain
² Instituto de Biotecnología de León (INBIOTEC), Avda. Real, 1. 24006 León, Spain
E-mail: jf.martin@unileon.es
Abstract: Clavaric acid is a potent antitumor agent produced by the mushroom-forming basidiomycete Hypholoma sublateritium. Clavaric acid is structurally similar to fasciculic acid, a related triterpenoid produced by Hypholoma fasciculare that is described as a calmodulin inhibitor.
These two compounds are derived from squalene by the action of enzymes that convert squalene to 2,3-dioxidesqualene and this intermediate to clavarinone, a direct precursor of clavaric acid or fasciculic acid. One of these enzymes, the squalene oxidase, is common for primary metabolism (ergosterol biosynthesis) and secondary metabolism, whereas the late enzymatic steps are specific for the biosynthesis of clavaric acid and fasciculic acid. Molecular genetics studies allowed us to clone and characterise the genes encoding these enzymes. These studies have provided a considerable insight into the biosynthesis of triterpenoids in fungi, providing new potent pharmacologically-active compounds. Squalene epoxidases and oxidosqualene cyclases with modified consensus motifs in their active centers appear to play an important role in determining the oxidation and modification reactions that may result in specific secondary metabolites.

Manuscript ID: molecules-triterp-20080930-us-Nes
Type of Paper: Article
Title: Steroidal Triterpenes: Design of Substrate-based Inhibitors of Ergosterol and Sitosterol Synthesis
Authors: Jialin Liu and W. David Nes
Affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX 79409, USA
E-mail: WDNES@aol.com
Abstract: This article reviews the design and study, in our own laboratory and in other laboratories, of new steroidal triterpenes with a modified lanosterol or cycloartenol frame. These compounds, along with a number of known analogs with the cholestane skeleton, have been evaluated as reversible or irreversible inhibitors of sterol C-24 methyltransferase (SMT) from plants, fungi and protozoa. The SMT catalyzes the C24-methylation reaction involved with the introduction of the C24-methyl group of ergosterol and the C24-ethyl group of sitosterol, cholesterol surrogates that function as essential membrane inserts in many photosynthetic and non-photosynthetic eukaryotic organisms. Sterol side chains constructed with a nitrogen, sulfur, bromine or fluorine atom or altered to possess a methylene cyclopropane group, or elongated to include terminal double or triple bonds are shown to exhibit different in vitro activities toward the SMT which are mirrored in the inhibition potencies detected in the growth response of treated cultured human and plant cells or microbes. Several of the substrate-based analogs surveyed here appear to be taxa-specific compounds acting as mechanism-based inactivators of the SMT, a crucial enzyme not synthesized by animals. Possible mechanisms for the inactivation process and generation of novel products catalyzed by the variant SMTs are discussed.

Manuscript ID: Molecules-triterp-20081024-Akhmetova
Type of paper: Review
Title: Pentacyclic Triterpenes and Their Synthetic Transformations
Authors: Vnira R. Akhmetova, Elvira R. Shakurova
Affiliciation: Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, 141 prosp. Oktyabrya, 450075, Ufa, Russian Faderation.
E-mails: vnirara@mail.ru, shakurovaer@mail.ru,ink@anrb.ru
Abstract: Literary data on polycyclic triterpenoids and own experimental results on separation, X-ray researches and synthetic transformations of pentacyclic triterpenoids from Scotch thistle Onopordum acanthium L. growing in the south of the Ural mountains (Russia) are generalized.
Triterpenoids rather widespread occure in nature. Their molecules containing six isoprenoid links, are predecessors of steroids, both in animals, and in plant organisms. Practically all plants produce tetra-and pentacyclic triterpenes metabolites with various types of a carbon skeleton. Among pentacyclic triterpenes 10 structural types are revealed. In a medical practice pentacyclic triterpenoids are already successfully applied in composition of regulators of cardiovascular system, antibacterial and anti-AIDS preparations, and in glycosylate form (saponin) in composition of hypochilesterinemic preparations and for hemosorption superfluous serum cholesterin from blood. Complete biological potential of polycyclic triterpenoids as medical products is still not studied. In this review there were summaried the various types of plant pentacyclic triterpenoids that have been described in the literature, such as oleanane, ursane, taraxastane and lupan (section 1); information about on biological activity (section 2), and also information available in the literature about chemical modifications triterpenoids and biological activity of their synthetic analogues (section 3). In the present review literary information for the past of 15-20 years is observed. The bibliographic list contains about 150 titles.

Manuscript ID: molecules-triterp-20081030-es-Palazon
Type of paper: Review
Title: Steroidal lactones from Withania somnifera, an ancient plant for novel medicine.
Authors: Elisabeth Moyano ¹, M. Hossein Mirjalili ², Mercedes Bonfill ³, Rosa M. Cusido ³, Javier Palazón ^3,*
Affiliations: ¹ Departament de Ciencies Experimentals i de la Salut. Universitat Pompeu Fabra. Av. Doctor Aiguader 80. 08003 Barcelona. Spain.
² Medicinal Plants and Drugs Research Institute, Shaid Behesti University, Evin, Tehran. Iran.
³ Laboratori de Fisiologia Vegetal. Facultat de Farmacia. Universitat de Barcelona. Av. Joan XXIII s/n. 08028 Barcelona. Spain.
E-mail: javierpalazon@ub.edu
Abstract: Whitania somnifera, commonly known as Ashwagandha, is an important medicinal plant used in Ayurvedic and indigenous medicine for over 3000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of these plants, the withanolides, are a group of triterpenoids occurring C₂₈-steroidal lactones built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years numerous pharmacological investigations have been carried out based on the components of W. somnifera extracts. We present here an overview about the chemical structures of triterpenoid components and their biological activity focusing on two novel activities, the tumor inhibition and antiangiogenic activity of withaferin A and the effects of withanolide A in Alzheimer's disease. The last attempts for biotechnological production of withanolides also are commented.

Manuscript ID: molecules-triterp-20090115-sg-Popovich
Title: Chemical and Biological Characterization of Oleanane Triterpenoids from Soy
Authors: Wei Zhang and David G. Popovich*
Affiliation: Department of Chemistry, National University of Singapore, Science Drive 4, Singapore, 117543
*Author to whom correspondence should be addressed; Tel: (65) 6516 4695; Fax: (65) 6775 7895; E-mail: chmpdg@nus.edu.sg
Abstract: Soyasaponins are a group of complex and structural diverse oleanane triterpenoids found in soy (Glycine max) and other legumes. Soyasaponins are primarily classified into two main groups, group A and B, based on the attachment of sugar moieties at position C-3 and C-22 of ring structures. Group B soyasaponins are further classified into two subcategories known as of 2,3-dihydro-2, 5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) and non DDMP conjugated molecules. At least eight group A and ten group B soyasaponins have been reported in the literature, however determining the genuine soyasaponins are hampered by a number of reported artifacts created during processing, extraction and storage of soy. Furthermore, isolation of soyasaponins is complicated by the presence of the bioactive soy isoflavones which often overlap with saponin polarity. Soyasaponins have been reported to have cholesterol lowering, anticancer, antiviral and hepatoprotective properties. Extracts, aglycones of group A and B and individual group B soyasaponins such as soyasaponin I have been reported to posses specific bioactivies such as modulating the cell cycle and inducing apoptosis in cell culture studies. The isolation, chemical characterization and detection strategies by HPLC and LC-MS to produce group B soyasaponins will be reviewed along with a detailed review of reported bioactive effects of soyasaponins extracts and individual molecules.

Type of Paper: Review
Title: Squalene Emulsions for Parenteral Vaccine and Drug Delivery
Authors: Christopher B. Fox, James Chesko, Thomas S. Vedvick*
Affiliation: Infectious Disease Research Institute, 1124 Columbia St, Ste 400, Seattle, WA 98104, USA, *Corresponding author. Phone: 1-206-330-2530 Fax: 1-206-381-3678, Email: tvedvick@idri.org
Abstract: Squalene is a linear triterpene that is becoming increasingly utilized as a principal component of parenteral emulsions for drug and vaccine delivery. In this review, the chemical structure and various sources of squalene are discussed. Moreover, the physicochemical and biological properties of squalene-containing emulsions are evaluated in the context of parenteral formulations. Historical and current parenteral emulsion products containing squalene are reviewed. Finally, analytical techniques for squalene concentration quantitation, structure elucidation, and emulsion interactions are examined.