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The genus Maytenus is a member of the Celastraceae family, of which several species have long been used in traditional medicine. Between 1976 and 2021, nearly 270 new compounds have been isolated and elucidated from the genus Maytenus . Among these, maytansine and its homologues are extremely rare in nature. Owing to its unique skeleton and remarkable bioactivities, maytansine has attracted many synthetic endeavors in order to construct its core structure. In this paper, the current status of the past 45 years of research on Maytenus , with respect to its chemical and biological activities are discussed. The chemical research includes its structural classification into triterpenoids, sesquiterpenes and alkaloids, along with several chemical synthesis methods of maytansine or maytansine fragments. The biological activity research includes activities, such as anti-tumor, anti-bacterial and anti-inflammatory activities, as well as HIV inhibition, which can provide a theoretical basis for the better development and utilization of the Maytenus .

Background: Lychnophora trichocarpha (Spreng.) Spreng. ex Sch.Bip has been used in folk medicine to treat pain, inflammation, rheumatism and bruises. Eremantholide C, a sesquiterpene lactone, is one of the substances responsible for the anti-inflammatory and anti-hyperuricemic effects of L. trichocarpha., Objectives: Considering the potential to become a drug for the treatment of inflammation and gouty arthritis, this study evaluated the permeability of eremantholide C using in situ intestinal perfusion in rats. From the permeability data, it was possible to predict the fraction absorbed of eremantholide C in humans and elucidate its oral absorption process., Methods: In situ intestinal perfusion studies were performed in the complete small intestine of rats using different concentrations of eremantholide C: 960 μg/ml, 96 μg/ml and 9.6 μg/ml (with and without sodium azide), in order to verify the lack of dependence on the measured permeability as a function of the substance concentration in the perfusion solutions., Results: Eremantholide C showed P eff values, in rats, greater than 5 × 10 -5  cm/s and fraction absorbed predicted for humans greater than 85%. These results indicated the high permeability for eremantholide C. Moreover, its permeation process occurs only by passive route, because there were no statistically significant differences between the P eff values for eremantholide C., Conclusion: The high permeability, in addition to the low solubility, indicated that eremantholide C is a biologically active substance BCS class II. The pharmacological activities, low toxicity and biopharmaceutics parameters demonstrate that eremantholide C has the necessary requirements for the development of a drug product, to be administered orally, with action on inflammation, hyperuricemia and gout.

The genus Curcuma is part of the Zingiberaceae family, and many Curcuma species have been used as traditional medicine and cosmetics in Thailand. To find new cosmeceutical ingredients, the in vitro anti-inflammatory, anti-oxidant, and cytotoxic activities of four Curcuma species as well as the isolation of compounds from the most active crude extract ( C. aromatica ) were investigated. The crude extract of C. aromatica showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity with an IC 50 value of 102.3 μg/mL. The cytotoxicity effect of C. aeruginosa, C. comosa, C. aromatica, and C. longa extracts assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay at 200 μg/mL were 12.1 2.9, 14.4 4.1, 28.6 4.1, and 46.9 8.6, respectively. C. aeruginosa and C. comosa presented apoptosis cells (57.7 3.1% and 32.6 2.2%, respectively) using the CytoTox-ONE™ assay. Different crude extracts or phytochemicals purified from C. aromatica were evaluated for their anti-inflammatory properties. The crude extract of C. aromatica showed the highest potential to inhibit NF-κB activity, followed by C. aeruginosa, C. comosa, and C. longa , respectively. Among the various purified phytochemicals curcumin, germacrone, curdione, zederone, and curcumenol significantly inhibited NF-κB activation in tumor necrosis factor (TNF) stimulated HaCaT keratinocytes. Of all compounds, curcumin was the most potent anti-inflammatory., Competing Interests: The authors declare no conflicts of interest.

Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids-teucdiol C ( 1 ), D ( 2 ), E ( 3 ), and F ( 4 ), together with two known sesquiterpenoids teucdiol B ( 5 ) and epi-guaidiol A ( 6 )-were obtained from its fermented broth of T. albuminosus . Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction. Epi -guaidiol A showed obvious anti-acetylcholinesterase activity in a dose-dependent manner. The experimental results displayed that T. albuminosus possess the pharmaceutical potential for Alzheimer's disease, and it was an effective way to dig new pharmaceutical agent of T. albuminosus with the microbial fermentation technique., Competing Interests: The authors declare no conflict of interest.

Heat stress affects the yield of medicinal plants and can reduce biomass and/or metabolite production. In order to evaluate the effect of heat-induced stress on the essential oil production in Menth a x p iper ita L. var. Mitcham (Mitcham mint) and Mentha arvensis var. piperascens Malinv. ex L. H. Bailey (Japanese mint), we studied the chemical composition of the oils of the two mint species under different heat shock stresses in growth chambers. The antibacterial activity of the essential oils was also evaluated; microscopic observation (fluorescence and electron transmission) was used to assess the effect of the tested samples on bacterial growth. The results obtained shed light on the mint essential oils composition and biological activity in relation to heat stress., Competing Interests: The authors declare no conflict of interest.

Abnormal multiplication of oral bacteria causes dental caries and dental plaque. These diseases continue to be major public health concerns worldwide, mainly in developing countries. In this study, the chemical composition and antimicrobial activity of the essential oil of Vitex agnus-castus leaves (VAC‒EO) collected in the North of Brazil against a representative panel of cariogenic bacteria were investigated. The antimicrobial activity of VAC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by using the broth microdilution method in 96-well microplates. The chemical constituents of VAC-EO were identified by gas chromatography (GC‒FID) and gas chromatography‒mass spectrometry (GC‒MS). VAC‒EO displayed some activity against all the investigated oral pathogens; MIC values ranged from 15.6 to 200 μg/mL. VAC-EO had promising activity against Streptococcus mutans (MIC= 15.6 μg/mL), Lactobacillus casei (MIC= 15.6 μg/mL), and Streptococcus mitis (MIC= 31.2 μg/mL). The compounds 1,8-cineole (23.8%), (E)-β-farnesene (14.6%), (E)-caryophyllene (12.5%), sabinene (11.4%), and α-terpinyl acetate (7.7%) were the major chemical constituents of VAC‒EO. VAC-EO displays antimicrobial activity against cariogenic bacteria. The efficacy of VAC-EO against S. mutans is noteworthy and should be further investigated.

Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system (CNS) in adults. Multidrug resistance (MDR) results in undesirable prognosis during GBM chemotherapy. In this study, we determined that Radicol (RAD), a novel trinorguaiane-type sesquiterpene originally isolated from the root of Dictamnus radicis Cortex, exhibited potently cytotoxic effect on temozolomide (TMZ)-resistant GBM cell lines in a dose-dependent manner. Radicol-induced apoptosis was confirmed with Hoechst 33342/propidium iodide and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labelling (TUNEL) staining. Studies investigating the mechanism revealed that RAD triggered an attenuation of protein disulphide isomerase (PDI) and induced the unmitigated unfolded protein response (UPR) and lethal endoplasmic reticulum (ER) stress. Simultaneously, we further demonstrated that RAD suppressed the activation of Akt/mTOR/p70S6K phosphorylation by up-regulating the induction of glycogen synthase kinase-3β (GSK-3β). These results established a link between RAD-induced ER stress and inhibition of the Akt/mTOR/p70S6K pathway, and the attenuation of PDI and activation of GSK-3β might be the synergistic target of antineoplastic effects during RAD-induced apoptosis. These findings suggested that RAD, possessing multiple cytotoxicity targets, low molecular weight and high lipid solubility, could be a promising agent for the treatment of malignant gliomas. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

The methanol extract of the leaves of Illicium lanceolatum, indigenous to Fujian Province, People's Republic of China, was found to exhibit antimicrobial activity against the periodontal pathogen Porphyromonas gingivalis, and a bioassay-guided fractionation led to the isolation of two new compounds, 1 and 2, along with two known santalane-type sesquiterpenoids, 3 and 4. The structures of lanceolactone A (1) and lanceolactone B (2) were elucidated by analyzing their 2D NMR spectroscopic data. Compounds 1 and 2 were assigned as new tetranorsesquiterpenoids with a spiroacetal ring and tricyclic structure, respectively. Compound 3 (α-santal-11-en-10-one) showed potent antimicrobial activity against the oral pathogen P. gingivalis.

Four commercial qualities of Hawaiian sandalwood oil produced from wood of Santalum paniculatum originating from the island of Hawaii ("The Big Island") were analyzed using GC and GC-MS. Main constituents of the oils were (Z)-α-santalol (34.5-40.4%) and (Z)-β-santalol (11.0-16.2%). An odor evaluation of the oils was carried out against East Indian sandalwood oil. In addition, the chemical composition of Hawaiian sandalwood oil was compared with four different Santalum species originating from East India, New Caledonia, Eastern Polynesia and Australia, respectively.

Plant secondary metabolites are known to not only play a key role in the adaptation of plants to their environment, but also represent an important source of active pharmaceuticals. Alpinia oxyphylla capsular fruits, made up of seeds and pericarps, are commonly used in traditional East Asian medicines. In clinical utilization of these capsular fruits, inconsistent processing approaches (i.e., hulling pericarps or not) are employed, with the potential of leading to differential pharmacological effects. Therefore, an important question arises whether the content levels of pharmacologically active chemicals between the seeds and pericarps of A. oxyphylla are comparable. Nine secondary metabolites present in A. oxyphylla capsular fruits, including flavonoids (e.g., tectochrysin, izalpinin, chrysin, apigenin-4',7-dimethylether and kaempferide), diarylheptanoids (e.g., yakuchinone A and B and oxyphyllacinol) and sesquiterpenes (e.g., nootkatone), were regarded as representative constituents with putative pharmacological activities. This work aimed to investigate the abundance of the nine constituents in the seeds and pericarps of A. oxyphylla. Thirteen batches of A. oxyphylla capsular fruits were gathered from different production regions. Accordingly, an ultra-fast high performance liquid chromatography/quadrupole tandem mass spectrometry (UFLC-MS/MS) method was developed and validated. We found that: (1) the nine secondary metabolites were differentially concentrated in seeds and fruit capsules; (2) nootkatone is predominantly distributed in the seeds; in contrast, the flavonoids and diarylheptanoids are mainly deposited in the capsules; and (3) the content levels of the nine secondary metabolites occurring in the capsules varied greatly among different production regions, although the nootkatone levels in the seeds were comparable among production regions. These results are helpful to evaluating and elucidating pharmacological activities of A. oxyphylla capsular fruits. Additionally, it may be of interest to elucidate the mechanisms involved in the distinct accumulation profiles of these secondary metabolites between seeds and pericarps.

A sporadic seasonal neurotoxic food poisoning, unique to northern parts of New Zealand, especially The Bay of Plenty, has recurred-with implications for our primary produce industry, as well as human health.

The production and trade of Indian sandalwood oil is strictly regulated, due to the impoverishment of the plantations; for such a reason, Australian sandalwood oil has been evaluated as a possible substitute of the Indian type. International directives report, for both the genuine essential oils, specific ranges for the sesquiterpene alcohols (santalols). In the present investigation, a multidimensional gas chromatographic system (MDGC), equipped with simultaneous flame ionization and mass spectrometric detection (FID/MS), has been successfully applied to the analysis of a series of sandalwood oils of different origin. A detailed description of the system utilized is reported. Three santalol isomers, (Z)-α-trans-bergamotol, (E,E)-farnesol, (Z)-nuciferol, epi-α-bisabolol and (Z)-lanceol have been quantified. LoD (MS) and LoQ (FID) values were determined for (E,E)-farnesol, used as representative of the oxygenated sesquiterpenic group, showing levels equal to 0.002% and 0.003%, respectively. A great advantage of the instrumental configuration herein discussed, is represented by the fact that identification and quantitation of target analytes are carried out in one step, without the need to perform two separate analyses., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We report the structures and stereochemistry of seven bisabolyl-derived sesquiterpenes arising from an unprecedented 1,6-cyclization (cisoid pathway) efficiently catalyzed by tobacco 5-epi-aristolochene synthase (TEAS). The use of (2Z,6E)-farnesyl diphosphate as an alternate substrate for recombinant TEAS resulted in a robust enzymatic cyclization to an array of products derived exclusively (>/=99.5%) from the cisoid pathway, whereas these same products account for ca. 2.5% of the total hydrocarbons obtained using (2E,6E)-farnesyl diphosphate. Chromatographic fractionations of extracts from preparative incubations with the 2Z,6E substrate afforded, in addition to the acyclic allylic alcohols (2Z,6E)-farnesol (6.7%) and nerolidol (3.6%), five cyclic sesquiterpene hydrocarbons and two cyclic sesquiterpene alcohols: (+)-2-epi-prezizaene (44%), (-)-alpha-cedrene (21.5%), (R)-(-)-beta-curcumene (15.5%), alpha-acoradiene (3.9%), 4-epi-alpha-acoradiene (1.3%), and equal amounts of alpha-bisabolol (1.8%) and epi-alpha-bisalolol (1.8%). The structures, stereochemistry, and enantiopurities were established by comprehensive spectroscopic analyses, optical rotations, chemical correlations with known sesquiterpenes, comparisons with literature data, and GC analyses. The major product, (+)-2-epi-prezizaene, is structurally related to the naturally occurring tricyclic alcohol, jinkohol (2-epi-prezizaan-7beta-ol). Cisoid cyclization pathways are proposed by which all five sesquiterpene hydrocarbons are derived from a common (7R)-beta-bisabolyl(+)/pyrophosphate(-) ion pair intermediate. The implications of the "cisoid" catalytic activity of TEAS are discussed.

A survey of individual specimens of northern Papua New Guinea derived Cacospongia mycofijiensis has yielded novel sesquiterpenes, aignopsanoic acid A (1), methyl aignopsanoate A (2), and isoaignopsanoic acid A (3). The structures and absolute configurations of 1-3 were established using NMR data, X-ray crystallography results, and an analysis of CD properties. Two of these metabolites, 1 and 2, were moderately active against Trypanosoma brucei, the parasite responsible for sleeping sickness.

Bisabolane-type sesquiterpenes are a class of biologically active compounds that has antitumour,antifungal, antibacterial,antioxidant and antivenom properties.We investigated the effect of two new highly oxygenated bisabolane-type sesquiterpenes (HOBS)isolated from Cremanthodium discoideum (C.discoideum) on tumour cells. Our results showed that HOBS induced morphological differentiation and reduced microvilli formation on the cell surface in SMMC-7721 cells.Flow cytometry analysis demonstrated that HOBS could induce cell-cycle arrest in the G1 phase. Moreover,HOBS was able to increase tyrosine-alpha ketoglutarate transaminase activity,decrease alpha- foetoprotein level and gamma-glutamyl transferase activity. In addition,we found that HOBS inhibited the anchorage- independent growth of SMMC-7721 cells in a dose-dependent manner.Taken together,all the above observations indicate that HOBS might be able to normalize malignant SMMC-7721 cells by inhibiting cell proliferation and inducing redifferentiation.

Three new dimeric sesquiterpenoids, chloramultilides B-D ( 1- 3), along with 10 known sesquiterpenoids, were isolated from the whole plant of Chloranthus spicatus. Their structures were established by physical data (1D and 2D NMR, MS). The structure and absolute configuration of 1 was confirmed by X-ray crystallography. Compound 1 exhibited moderate in vitro antifungal activity.

Sesquiterpene esters are the active principle in the medicinal plant Petasites hybridus. Two chemotypes, the petasin chemotype and the furanopetasin chemotype, are known, but only the first one is suitable for pharmaceutical purposes. Experimental crossings were performed within and between plants of both chemotypes to study the genetic basis of the occurrence of these sesquiterpenes. The chemotype was determined by TLC in extracts of a small piece of rhizome in the parent plants and the progenies. A model including the combined action of two genes is proposed to explain the inheritance of the chemotypes where the furanopetasin chemotype is under recessive genetic control.

Five new humulane-type sesquiterpenes, mitissimols A (1), B (2), and C (3), and a mixture of mitissimol A oleate (4) and mitissimol A linoleate (5), were isolated from the fruiting bodies of Lactarius mitissimus. Their structures were elucidated on the basis of comprehensive spectroscopic techniques and necessary chemical methods. The relative stereochemistry of 1 was determined by single-crystal X-ray diffraction analysis.

Six new illudoid sesquiterpenes, russujaponols A-F (1-6), were isolated from the fruiting bodies of Russula japonica Hongo. Their structures were established primarily by 2D NMR experiments, and the structure of the main compound, russujaponol A (1), was confirmed by X-ray crystallographic analysis of its benzoate (1a). Russujaponol A (1) suppressed invasion of human fibrosarcoma (HT1080) cells into Matrigel in a concentration-dependent manner and caused 63% inhibition at 3.73 microM.

Chromatographic investigation of an acetone extract of the octocoral Xenia florida afforded three new xenicane diterpenes, namely, florxenilide A (1), florxenilide B (2), and florxenilide C (3), in addition to seven known xenicane diterpenes and two known cadinene sesquiterpenes. Structures were elucidated through spectroscopic analysis, especially 2D NMR, and chemical derivatization. The absolute configuration of 1 was determined by NOESY, CD, and Mosher's methods. Florxenilides A (1) and B (2) exhibited cytotoxicity against human colon cancer (WiDr) cells at 4.5 and 3.7 muM, respectively.

The Huperziaceae is comprised of two genera, Huperzia and Phlegmariurus. Because of the content of Lycopodium alkaloids like huperzine A, which are used to treat a number of human ailments, plants of the Huperziaceae are experiencing a rapid decline in China, mostly due to over-harvesting. Because of this trend, we engaged from 1995 to 2001 in an investigation of the natural resources of the Huperziaceae in China. The main objectives of this study were: to catalog Huperziaceae plant resources including the occurrence, general distribution, and abundance of the various Huperziaceae species in China; and to determine traditional use and pharmaceutical values of each species. Twenty-nine species, 2 varieties, and 2 forma of Huperzia and 19 species of Phlegmariurus were identified through field investigation, collection, visits with local traditional doctors, and review of specimens in herbaria and of the literature. Ethnobotanical studies of these plants revealed that 33 of these species are used by the local communities for medicinal purposes. One species, Huperzia serrata, is one of the most popular. As a result, it is observing the greatest decline, mandating a change in collection practice and general attitude towards these plants. Introduction of conservation plans and training of the local communities regarding appropriate collection practices of these plants and their marketing in China are required to reverse the trend of decline among these species. In addition, development of cultivation or other propagation practices, such as in vitro propagation, would have the added benefits of socio-economic uplift of the local communities and sustainability of this important source of huperzine A.

The process of formation of new vessels from pre-existing capillaries is called angiogenesis. Angiogenesis is a complex process which involves distinct cells, soluble components and factors related to the extra-cellular matrix and which is highly important in a large variety of physiological and pathological processes in the body. Angiogenesis regulation takes place through a perfect equilibrium between the production and release of different stimulatory and inhibitory factors which vary in relation to needs and tissue types. A large number of diseases are characterized by alterations in the angiogenic process, either by an insufficiency or by excessive angiogenesis. The requirement of blood vessel proliferation for tumor growth was observed more than a century ago. Angiogenic treatment would have an indirect antitumoral action, inhibiting tumor vascularization and impairing the supply of essential nutrients for tumoral growth and development.

Microbial transformation of zaluzanin-D using different fungi gave 11,13-dihydrozaluzanin-C, zaluzanin-C, 4,16,11,13 - tetrahydro zaluzanin-C, estafiatone, dihydroestafiatol and dihydroestafiatone.

Malaria is the major parasitic infection in many tropical and subtropical regions, leading to more than one million deaths (principally young African children) out of 400 million cases each year (WHO world health report 2000). More than half of the world's population live in areas where they remain at risk of malaria infection. During last years, the situation has worsened in many ways, mainly due to malarial parasites becoming increasingly resistant to several antimalarial drugs. Furthermore, the control of malaria is becoming more complicated by the parallel spread of resistance of the mosquito vector to currently available insecticides. Discovering new drugs in this field is therefore a health priority. Several new molecules are under investigation. This review describes the classical treatments of malaria and the latest discoveries in antimalarial agents, especially artemisinin and its recent derivatives as well as the novel peroxidic compounds.

Five sesquiterpene carbonimide dichlorides (1-5) have been isolated from the dichloromethane extract of the Australian sponge Ulosa spongia. The structures of the two new compounds, ulosins A (1) and B (2), were elucidated by employing spectroscopic techniques (NMR, MS, UV, and IR). The chemotaxonomic significance of our data is discussed.

Artemisinin derivatives are an important new class of antimalarial agents. These compounds contain endoperoxide bridges which are essential for antimalarial activity. Artemisinin is believed to act via a two-step mechanism. Artemisinin is first activated by intraparasitic heme-iron which catalyzes the cleavage of this endoperoxide. A resulting free radical intermediate may then kill the parasite by alkylating and poisoning one or more essential malarial protein(s). No clinically relevant artemisinin-resistant human malaria has yet been reported. However, an artemisinin-resistant strain of murine malaria has been developed and may offer clues to the kinds of resistance that may someday develop in human malarias.

FR65814, a novel immunosuppressant, was isolated from the cultured broth of Penicillium jensenii F-2883. The structure was assigned to be 5,6-dihydroxy-4-(1,2-epoxy-1,5-dimethyl-4-hexenyl)-1-oxaspiro++ +[2,5]octane by spectroscopic analyses. The compound suppressed the immune response at low concentration. In addition, a structually related component fumagillol, a known carcinolytic agent, was also isolated and found to show immunosuppressive activity.