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Two new maytansinoids from maytenus buchananii

Reinvestigation of fractions derived from large-scale fractionation of Maytenus buchananii led to the isolation of two new maytansinoids. The structures of these principles were determined using electrospray MS, 1H NMR, 13C NMR, and 2D NMR techniques. One principle was found to be 2'-N-demethylmaytanbutine (2), while the other was found to be maytanbicyclinol (3), the first maytansinoid with two macrocyclic rings to be isolated from a Maytenus species.

Journal Article↗

Insect growth regulator and insecticidal activity of beta-dihydroagarofurans from Maytenus spp. (Celastraceae).

From the aerial parts of Maytenus disticha, we have isolated 9beta-benzoyloxy-1alpha,2alpha,6beta,8alpha,15penta-acetoxy-dihydro-beta-agarofuran (1) and from seeds of Maytenus boaria 9beta-furoyloxy-1alpha,6beta,8alpha-triacetoxy-dihydro-beta-agarofuran (2). These compounds and their MeOH and hexane/ethyl acetate (1:1 v/v) extracts were evaluated for their effects on the fall armyworm (Spodoptera frugiperda). Toosendanin, a commercial insecticide derived from Melia azedarach was used as a positive control. When tested for activity using neonate larvae in a nochoice artificial diet bioassays, the agarofurans 1, 2 and toosendanin as well as the MeOH and hexane/EtOAc extracts caused significant growth inhibitory effects with GC50 of 7.55; 3.84; 1.75; 14.0 and 7.3 ppm at 7 days, respectively. Compounds 1 and 2 caused 100% larval mortality at 25 and 15 ppm, respectively. MeOH and hexane/EtOAc extracts caused 100% larval mortality at 25.0 ppm, respectively, they also increased the development time of surviving larvae and a significant delay for the time of pupation and adult emergence. These compounds showed comparable potency of activity with toosendanin. Acute toxicity against adults of S. frugiperda was also found, for hexane/EtOAc extract and 2 had the most potent activity with LD50 value of 4.7 and 1.9 ppm, respectively. MeOH extract, hexane/EtOAc extract, 1 and 2 caused acetylcholinesterase inhibition with 78.0, 89.2, 79.3 and 100% inhibition at 15.0 ppm, respectively. Therefore, the furoyloxy agarofuran may be responsible for the insecticidal activity of these plants.

Animals↗

Chemical constituents from the infusion of Zollernia ilicifolia Vog. and comparison with Maytenus species.

The new flavonoid glycoside kaempferol-3-O-alpha-L-rhamnopyranosyl(1-->2)-O-[alpha-L-rhamnopyranosyl(1-->6)]-O-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside was isolated together with (S)-zierin from the leaves of Zollernia ilicifolia (Fabaceae), a medicinal plant used as analgesic and antiulcerogenic effects in Brazilian Tropical Atlantic Rain Forest. The structures were established on the basis of 1H, 13C NMR and 2D NMR (COSY, HMBC, HMQC), UV, MS and IV spectra. The infusion of Zollernia ilicifolia was qualitatively compared to the infusion of the espinheiras-santas (Maytenus aquifolium and Maytenus ilicifolia) by HPLC-DAD.

Brazil↗

[The search for cytostatic substances in the tissues of plants of the genus Maytenus molina in in vitro culture. I. Callas culture and biological studies of its extracts].

Plant tissue cultures of Maytenus wallichiana Raju et Babu and Maytenus emarginata Ding Hou were initiated. Growth conditions of the callus and the optimum medium composition have been established. Increments of callus wet mass and dynamics of callus growth were determined. Morphological and microscopic observations were also performed. The most efficient growth of the callus, resulting in increments of its wet mass up to 6460%, was obtained on the modified Murashige and Skoog medium. Extracts of the callus were found to be inactive against microorganisms, but proved cytotoxic for lymphocytic leukaemia L 5178Y (ED50 18-48 micrograms/cm3) and the protozoon T. pyriformis (ID50 43-53 micrograms/cm3).

Animals↗

Nine new isoxuxuarine-type triterpene dimers from Maytenus chuchuhuasca.

Nine new isoxuxuarine-type triterpene dimers, named isoxuxuarines B alpha (1), B beta (2), 7,8-dihydro-B alpha (3), C alpha (4), C beta (5), 7,8-dihydro-C alpha (6), D alpha (7), D beta (8), and 7,8-dihydro-D alpha (9), were isolated from the South American medicinal plant 'xuxuá' (Maytenus chuchuhuasca). The structures were elucidated on the basis of several spectroscopic analyses, including 2D-NMR experiments, MS spectra, and CD spectral studies. The isolations and structure elucidations of the new triterpene dimers are presented, and a rationale for the divergent formation of the regiochemical and stereochemical isomers of triterpene dimers is discussed.

Dimerization↗

New chemical constituents from the endophyte Streptomyces species LR4612 cultivated on Maytenus hookeri.

From solid cultures of the biologically important endophyte Streptomyces species LR4612, cultivated on Maytenus hookeri, four new and two known compounds were isolated. The new compounds were identified as (2S*,3S*)-5-amino-3-hydroxy-5-oxopentan-2-yl 3-(formylamino)-2-hydroxybenzoate (1), N-[(3R*,4R*)-3-amino-3,4-dihydro-4-methyl-2,6-dioxo-2H,6H-1,5-benzodioxocin-10-yl]formamide (2), (5beta,6alpha)-6,11-dihydroxyeudesmane (3), and 5-(6,7-dihydroxy-6-methyloctyl)furan-2(5H)-one (4); the known compounds were elucidated as sorbicillin (5) and N-acetyltyramine (6). The structures were established by HR-ESI-MS and in-depth NMR analyses.

Maytenus↗

Structural determination of 3beta-stearyloxy-urs-12-ene from Maytenus salicifolia by 1D and 2D NMR and quantitative 13C NMR spectroscopy.

Six pentacyclic triterpenoids, 3beta-stearyloxy-urs-12-ene (1), friedelin (2), 3beta-friedelinol (3), alpha-amyrin (4), beta-amyrin (5), and lupeol (6), have been isolated from the hexane extract of Maytenus salicifolia Reissek (Celastraceae) leaves. The molecular and structural formula as well as the stereochemistry of a new pentacyclic triterpene (1) were determined using data obtained from 1H and 13C NMR spectra, DEPT135 and by 2D HSQC, HMBC, COSY and NOESY experiments. The molecular formula C48H84O2 was established using quantitative 13C NMR, and the molecular weight (692 Da) was confirmed by elemental analysis and mass spectrometry (GC-MS).

Carbon Isotopes↗

Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography.

Five different morphological types of Maytenus ilicifolia of the same age and harvested under the same conditions showed distinct accumulations of some friedo-nor-oleananes. A rapid, sensitive and reliable reverse-phase HPLC method (employing an external standard) was used for the determination of the cytotoxic triterpenoids, 20 alpha-hydroxymaytenin, 22 beta-hydroxymaytenin, maytenin, celastrol and pristimerin in each of the five types. Well resolved peaks with good detection response and linearity in the range 1.0-100 micrograms/mL were obtained.

Antineoplastic Agents, Phytogenic↗

Antioxidant flavan-3-ols and flavonol glycosides from Maytenus aquifolium.

TLC autographic assay revealed, in the EtOAc extract obtained from leaves and root bark of Maytenus aquifolium (Celastraceae), the presence of fi ve compounds exhibiting antioxidant properties towards beta-carotene. They were isolated and identified as epigallocatechin (1), (+) ouratea-catechin (2), proanthocyanidin (3), kaempferol 3-O-alpha-L-rhamnopyranosyl (1-->6)-O-[beta-D-glucopyranosyl (1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl (4) and quercetin 3-O-alpha-L-rhamnopyranosyl (1-->6)-O-[beta-D-glucopyranosyl (1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)]-O-beta-D-glucopyranosyl (5). The isolates were investigated for their redox properties using cyclic voltammetry and for their radical scavenging abilities through spectrophotometric assay on the reduction of 2,2-diphenyl-pycryl hydrazyl (DPPH). These results were correlated to the inhibition of beta-carotene bleaching on TLC autographic assay and to structural features of the flavonoids.

Antioxidants↗

A lyophilized aqueous extract of Maytenus ilicifolia leaves inhibits histamine-mediated acid secretion in isolated frog gastric mucosa.

Lyophilized aqueous extract of Maytenus ilicifolia leaves (LAEMIL) is commonly used in Brazilian folk medicine in the treatment of dyspepsia as well as gastric ulcers. We have investigated the effect and the possible mechanism of action of the LAEMIL on acid secretion in isolated frog gastric mucosa incubated in an Ussing chamber. It was observed that LAEMIL (7-28 mg%) as well as cimetidine (125-4,000 microM), a well-known histamine H2 receptor antagonist, decreased basal acid secretion in a concentration-dependent manner. Similarly to cimetidine (190 microM), LAEMIL (21 mg%) also inhibited gastric acid secretion induced by increasing concentrations of histamine (50-800 microM). The EC50 values for histamine alone and histamine in the presence of LAEMIL or cimetidine were 94.6 microM (71.1-125.9 microM), 244.9 microM (209.4-286.4 microM) and 142.2 microM (23.6-855.0 microM), respectively. LAEMIL, histamine and cimetidine were effective on acid secretion only when added to the serosal surface of the mucosa. Furthermore, simultaneous addition of LAEMIL and cimetidine at concentrations, per se, ineffective, caused a 16% reduction in the basal acid secretion [from 8.3 +/- 0.3 to 6.9 +/- 0.2 microEq g(-1) (15 min)(-1), n=4]. Although effects such as inhibition of histamine biosynthesis and/or histamine release can not be ruled out, our data suggest that LAEMIL, like cimetidine, reduces acid secretion in the isolated frog gastric mucosa by antagonising histamine H2 receptors.

Animals↗

Extraction and characterization of volatile compounds in Maytenus ilicifolia, using high-pressure CO2.

This work is focused on the chemical characterization of Maytenus ilicifolia extracts obtained from high-pressure CO2 extraction. The experiments were performed in a laboratory-scale unit, where the effect of particle size (35-200 mesh), CO2 mass flow rate (1-3 g/min), temperature (293-323 K), pressure (100-250 bar), and extraction time was investigated in terms of liquid yield and chemical composition of the extracts. Results show that the particle size and CO2 mass flow rate did not affect the liquid yield, whereas the extraction temperature and solvent density exerted a pronounced effect on both liquid yield and chemical distribution of volatile compounds. The extracts were chemically analyzed with regard to phytol, squalene, vitamin E, stigmasterol, friedelan-3-ol, friedelin, dodecanoic acid and geranyl acetate in a GC/MSD.

Brazil↗

Stem and leaf morphoanatomy of Maytenus ilicifolia.

Maytenus ilicifolia is a woody medicinal plant, employed mainly for its antiulcerogenic properties. The stem and leaf morphoanatomy has been studied, aiming to supply knowledge for the pharmacognostic and taxonomic species identification. The vegetative material was fixed, freehand sectioned and stained according to usual microtechniques. The stem organization, in secondary growth, shows periderm beneath the remaining epidermis, conspicuous sclerenchymatic ring in the cortex and cambium forming phloem outside and xylem inside. The leaf is simple, alternate and lanceolate and has sparsely spiny teeth along the margin. Epidermal cells containing calcium oxalate crystals, thick cuticle that forms cuticular flanges, dorsiventral mesophyll and amphicrival bundle in the midrib and petiole are observed.

Anti-Ulcer Agents↗

Antioxidant activity of Maytenus ilicifolia root bark.

Maytenus ilicifolia is an important plant with potential on cancer treatment and has been largely used in Brazil and other countries. We have evaluated the crude ethanolic extract of M. ilicifolia as a potential antioxidant source using an assay based on the bleaching of the radical monocation 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(*+)) and by HOCl scavenger capacity. Trolox and uric acid were used as positive controls. The results indicated M. ilicifolia root bark as a great source of antioxidants based on its potential as scavenger of radicals.

Antioxidants↗

Antimutagenic, antioxidant and antimicrobial properties of Maytenus krukovii bark.

The hydroalcoholic extract of Maytenus krukovii bark was investigated for its in vitro mutageno-protective activities by means of the Ames Salmonella/microsome assay. The extract showed an inhibitory effect in both T98 and T100 strains against the mutagenic activity of promutagen 2-aminoanthracene but was not protective against directly acting mutagens sodium azide and 2-nitrofluorene. When tested as a radical scavenger and antioxidant it produced a dose-dependent inhibition. The extract did not show significant antibacterial properties, and was weakly active against dermatophyte and phytopathogenic fungi, but inhibited the growth of phytopathogen Pithyum ultimum.

Animals↗

Technical aspects of the production of dried extract of Maytenus ilicifolia leaves by jet spouted bed drying.

This work presents an evaluation of the performance of jet spouted bed with inert particles for production of dried extracts of Maytenus ilicifolia leaves. The development of the extraction procedure was carried-out with the aid of three factors and three levels Box-Behnken design. The effects of the extraction variables, temperature (Text); stirring time (theta); and the ratio of the plant to solvent mass (m(p)/m(s)) on the extraction yield were investigated. The drying performance and product properties were evaluated through the measurement of the product size distribution, loss on drying (Up), flavonoid degradation (D) and, process thermal efficiency (eta). These parameters were measured as a function of the inlet temperature of the spouting gas (Tgi), the feed mass flow rate of the concentrated extract relative to mass flow rate of the spouting gas (Ws/Wg), the ratio between the feed flow rate of spouting gas relative to feed flow rate at a minimum spouting condition (Q/Qms) and the static bed height (H0). A powder product with a low degradation of active substances and good physical properties were obtained for selected operating conditions. These results indicate the feasibility of this drying equipment for the production of dried extracts of M. ilicifolia Martius ex Reiss leaves.

Brazil↗

Nitric oxide-dependent vasorelaxation induced by extractive solutions and fractions of Maytenus ilicifolia Mart ex Reissek (Celastraceae) leaves.

This study reveals that an ethanolic supernatant obtained from an aqueous extractive solution prepared from residues of methanolic extracts of ground leaves of Maytenus ilicifolia is able to cause a concentration- and endothelium-dependent relaxation in pre-contract rat aorta rings, with EC(50) of 199.7 (190-210) microg/ml. The non-selective nitric oxide synthase inhibitors l-NAME and l-NMMA abolished this effect, while superoxide dismutase and MnTBAP (a non-enzymatic superoxide dismutase mimetic) enhanced it. Further, relaxation induced by this ethanolic supernatant have been strongly inhibited by the guanylate cyclase inhibitors methylene blue and ODQ, as well as by the potassium channel blockers 4-aminopyridine and tetraethylammonium, but was unchanged by the cyclooxygenase inhibitor indomethacin and the membrane receptor antagonists atropine, HOE-140 and pirilamine. Partition of the ethanolic supernatant between H(2)O and EtOAc generated a fraction several times more potent, able to fully relax endothelium-intact aorta rings with an EC(50) of 4.3 (3.9-4.8) microg/ml. (13)C NMR spectrum of this fraction showed signals typical of catechin. This study reveals that the leaves of M. ilicifolia possess one or more potent substances able to relax endothelium-intact rat aorta rings, an event that appears to involve nitric oxide production, guanylate cyclase activation and potassium channel opening.

Animals↗

Development and validation of a LC-method for determination of catechin and epicatechin in aqueous extractives from leaves of Maytenus ilicifolia.

A reverse phase-LC method was developed and validated for separation and quantification of catechin and epicatechin in aqueous extractives from leaves of Maytenus ilicifolia. The analysis was performed using a C(18) column with acetic acid-acetonitrile gradient elution. The detection was carried out by UV at 280 nm and the peak identification was based on the retention times and by co-chromatography with reference substances. High coefficients of determination were achieved for both catechin and epicatechin peaks from the standard solutions (0.9996 and 0.9999), as well as from extractives (0.9981 and 0.9982, respectively). The method showed good repeatability (R.S.D. <1.5%), reproducibility (R.S.D. <5%) and good accuracy for both catechin and epicatechin peaks (101.4%, R.S.D. = 1.18% and 100.6%, R.S.D. = 2.07%, respectively).

Catechin↗

Anti-inflammatory activity of Maytenus senegalensis root extracts and of maytenoic acid.

Maytenus senegalensis (Lam.) Excell (Celastraceae) root extracts were investigated for their topical anti-inflammatory properties by measuring the inhibition of the Croton oil-induced ear oedema in mice. The highest anti-inflammatory activity was detected in the chloroform extract, which reduced the oedematous response with a potency similar to that of the NSAID reference drug indomethacin (ID(50)=84 and 93 microg/cm(2), respectively). Fractionation of the chloroform and of the hexane extracts led to the isolation of maytenoic acid (1), which exhibited a dose-dependent antiphlogistic effect (ID(50)=0.11 micromol/cm(2)) twice that of indomethacin (ID(50)=0.26 micromol/cm(2)) and only three times lower than that of hydrocortisone (ID(50)=0.04 micromol/cm(2)).

Animals↗