Synthesis and Cytotoxic Activity of Friedelinyl Esters.

Commonly isolated from plants of Celastraceae family, pentacyclic triterpenoids have a broad spectrum of biological activities, such as antitumor, anti-inflammatory, antinociceptive properties, among others. Structural modifications in these triterpenoids can enhance their biological activity, as well as their selectivity, while improving their physicochemical and pharmacokinetic aspects. In this study, eight novel esters were synthesized: four derivatives of 3α-friedelinol (friedelan-3α-yl p-bromobenzoate (1a); friedelan-3α-yl naproxenate (1b); friedelan-3α-yl pent-4-ynoate (1c); friedelan-3α-yl undec-10-ynoate (1d)) and four derivatives of 3ß-friedelinol (friedelan-3ß-yl p-bromobenzoate (2a); friedelan-3ß-yl naproxenate (2b); friedelan-3ß-yl pent-4-ynoate (2c); friedelan-3ß-yl undec-10-ynoate (2d)). Overall, 3α-friedelinol showed greater reactivity when compared to the ß-epimer. The esters 1b-d and 2b-c were tested for antileukemic activity against THP-1 and K-562 cells but showed low cytotoxicity for both cell lines. The most active against THP-1 cells was friedelan-3ß-yl naproxenate (2b, IC50=266±6 µM), and the most active against K-562 cells was friedelan-3α-yl pent-4-ynoate (1c, IC50=267±5 µM).

Phytochemical study of Magonia pubescens A. St.-Hil. and cytotoxicity of branches aqueous extract on breast cancer and leukemia cells.

Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL-1).

A methanol extract and N,N-dimethyltryptamine from Psychotria viridis Ruiz & Pav. inhibit Zika virus infection in vitro.

Zika virus (ZIKV) is a public health problem due to its association with serious fetal and neurological complications and the lack of antiviral agents and licensed vaccines against this virus. Surveillance studies have alerted about the potential occurrence of a new South American epidemic episode due to the recent circulation of an African ZIKV strain detected in Brazil. Therefore, it is essential to discover antiviral agents, including natural substances, that are capable of neutralizing the action of ZIKV. Several Psychotria species have antimicrobial and anti-inflammatory properties. Thus, a methanol extract and dimethyltryptamine from Psychotria viridis were evaluated for their ability to inhibit ZIKV infection in vitro by measuring the effective concentration that protects 50% of cells and investigating their possible mechanisms of action. The tested samples showed antiviral activity against ZIKV. The extract showed virucidal activity, affecting viral and non-cellular elements, inactivating the virus before infection or when it becomes extracellular after the second cycle of infection. It was also observed that both extract and dimethyltryptamine could inhibit the virus at intracellular stages of the viral cycle. In addition to dimethyltryptamine, it is believed that other compounds also contribute to the promising virucidal effect observed for the methanol extract. To our knowledge, this is the first report of the activity of a methanolic extract and dimethyltryptamine from Psychotria viridis against cellular ZIKV infection. These two samples, extracted from natural sources, are potential candidates for use as antiviral drugs to inhibit ZIKV infections.

Chemodiversity of Essential Oils from Nine Species of Celastraceae.

Extracts and compounds obtained from several species of Celastraceae family are reported as potential sources of drugs due to their diverse pharmacological properties. Nevertheless, essential oil composition from these species is still little known. This work aimed at the analysis of essential oils obtained from different Brazilian Celastraceae species. A total of seventeen oils were obtained using hydrodistillation process and analyzed by gas chromatography/mass spectrometry (GC/MS). Principal component analysis (PCA) allowed the identification of a chemical composition pattern among the analyzed essential oils. Some compounds were more frequent among Celastraceae species, such as cis- and trans-linalool oxide (14/17 oil samples), nerylacetone (13/17), linalool (11/17), ß-ionone (10/17), α-ionone (9/17), nerolidol (10/17), decanal (10/17), and dodecanoic acid (10/17). These results contribute to the chemophenetics of Celastraceae species.

Imines and lactones derived from friedelanes and their cytotoxic activity.

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol.

Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with ß-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with ß-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Antidiarrheal activity of extracts from Maytenus gonoclada and inhibition of Dengue virus by lupeol

ABSTRACT Diarrhea is an infectious disease caused by bacterial, virus, or protozoan, and dengue is caused by virus, included among the neglected diseases in several underdeveloped and developing countries, with an urgent demand for new drugs. Considering the antidiarrheal potential of species of Maytenus genus, a phytochemical investigation followed by antibacterial activity test with extracts of branches and heartwood and bark of roots from Maytenus gonoclada were conducted. Moreover, due the frequency of isolation of lupeol from Maytenus genus the antiviral activity against Dengue virus and cytotoxicity of lupeol and its complex with β-cyclodextrins were also tested. The results indicated the bioactivity of ethyl acetate extract from branches and ethanol extract from heartwood of roots of M. gonoclada against diarrheagenic bacteria. The lupeol showed potent activity against Dengue virus and low cytotoxicity in LLC-MK2 cells, but its complex with β-cyclodextrin was inactive. Considering the importance of novel and selective antiviral drug candidates the results seem to be promising.

Maytenus distichophylla and Salacia crassifolia: source of products with potential acetylcholinesterase inhibition

ABSTRACT The phytochemical study of the extract leaves from Maytenus distichophylla Mart. and Salacia crassifolia (Mart. ex Schult.) G. Don, Celastraceae, resulted in the isolation of 3-oxofriedelane, 3β-hydroxyfriedelane, 3β,24-dihydroxyfriedelane, 3-oxo-28,29-dihydroxyfriedelane, two mixtures of pentacyclic triterpenes (α-amyrin with β-amyrin and 3β-stearyloxy-urs-12-ene with 3β-stearyloxy-olean-12-ene), 3β-palmityloxy-urs-12-ene, the steroid β-sitosterol and its glycosylated derivative β-glucosyl-β-sitosterol, tritriacontanoic acid and the natural polymer gutta percha. The chemical structures of these constituents were established by IR, 1H and 13C NMR spectral data. Crude extracts, the mixtures of triterpenes and the isolated constituents were subjected to in vitro acetylcholinesterase inhibitory evaluation. Acetylcholinesterase inhibitory effect was observed for crude chloroform extract leaves from M. distichophylla (100%) and S. crassifolia (97.93 ± 5.63%) and for the triterpenes 3β,24-dihydroxyfriedelane (99.05 ± 1.12%), 3-oxo-28,29-dihydroxyfriedelane (90.59 ± 3.76%) and 3β-palmityloxy-urs-12-ene (97.93 ± 1.47%). The percent inhibitions induced by these natural products were very similar to those produced by physostigmine (93.94 ± 2.10%) a standard acetylcholinesterase inhibitor. Therefore, these results open perspectives for the use of these species as source of compounds with similar physostigmine pharmacological effect.

Psychotria viridis: Chemical constituents from leaves and biological properties.

The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and ß-sitosterol; the glycosylated steroids 3-O-ß-D-glucosyl-ß-sitosterol and 3-O-ß-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-ß-D-glucosyl-ß-sitosterol and 3-O-ß-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

Psychotria viridis: Chemical constituents from leaves and biological properties

ABSTRACT The phytochemical study of hexane, chloroform and methanol extracts from leaves of Psychotria viridis resulted in the identification of: the pentacyclic triterpenes, ursolic and oleanolic acid; the steroids, 24-methylene-cycloartanol, stigmasterol and β-sitosterol; the glycosylated steroids 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol; a polyunsaturated triterpene, squalene; the esters of glycerol, 1-palmitoylglycerol and triacylglycerol; a mixture of long chain hydrocarbons; the aldehyde nonacosanal; the long chain fat acids hentriacontanoic, hexadecanoic and heptadenoic acid; the ester methyl heptadecanoate; the 4-methyl-epi-quinate and two indole alkaloids, N,N-dimethyltryptamine (DMT) and N-methyltryptamine. The chemical structures were determined by means of spectroscopic (IR, 1H and 13C NMR, HSQC, HMBC and NOESY) and spectrometric (CG-MS and LCMS-ESI-ITTOF) methods. The study of biologic properties of P. viridis consisted in the evaluation of the acetylcholinesterase inhibition and cytotoxic activities. The hexane, chloroform, ethyl acetate and methanol extracts, the substances 24-methylene-cycloartanol, DMT and a mixture of 3-O-β-D-glucosyl-β-sitosterol and 3-O-β-D-glucosyl-stigmasterol showed cholinesterase inhibiting activity. This activity induced by chloroform and ethyl acetate extracts was higher than 90%. The methanol and ethyl acetate extracts inhibit the growth and/or induce the death of the tumor cells strains B16F10 and 4T1, without damaging the integrity of the normal cells BHK and CHO. DMT also demonstrated a marked activity against tumor cell strains B16F10 and 4T1.

New triterpenes from Maytenus robusta: structural elucidation based on NMR experimental data and theoretical calculations.

Leaves of Maytenus robusta (Celastraceae) were subjected to phytochemical investigation mainly directed at the isolation of pentacyclic triterpenes. The compounds friedelin (1), β-friedelinol (2), 3-oxo-21β-H-hop-22(29)-ene (7), 3,4-seco-friedelan-3,11β-olide (8), 3β-hydroxy-21β-H-hop-22(29)-ene (9), 3,4-seco-21β-H-hop-22(29)-en-3-oic acid (10), 3,4-seco-friedelan-3-oic acid (11), and sitosterol were identified in the hexane extract of M. robusta leaves. Compounds 8 and 9 are described herein for the first time. The structure and stereochemistry of both compounds were experimentally established by IR, HRLC-MS, and 1D (1H, 13C, and DEPT 135) and 2D (HSQC, HMBC and COSY) NMR data and supported by correlations with carbon chemical shifts calculated using the DFT method (BLYP/6-31G* level). Compounds 7 and 10 are also described for the first time, and their chemical structures were established by comparison with NMR data of similar structures described in the literature and correlations with BLYP/6-31G* calculated carbon chemical shifts. Compound 9, a mixture of 11 and sitosterol, and 3β,11β-dihydroxyfriedelane (4) were evaluated by the Ellman’s method and all these compounds showed acethylcholinesterase inhibitory properties.

Coordination of lapachol to bismuth(III) improves its anti-inflammatory and anti-angiogenic activities.

Complex [Bi(Lp)(2)]Cl was obtained with 4-hydroxy-3-(3-methylbut-2-enyl)naphthalene-1,2-dione, "lapachol" (HLp). Lapachol, [Bi(Lp)(2)]Cl and BiCl(3) were evaluated in a murine model of inflammatory angiogenesis induced by subcutaneous implantation of polyether polyurethane sponge discs. Intraperitoneal (i.p.) administration of lapachol or [Bi(Lp)(2)]Cl reduced the hemoglobin content in the implants suggesting that reduction of neo-vascularization was caused by lapachol. In the per os treatment only [Bi(Lp)(2)]Cl decreased the hemoglobin content in the implants. Likewise, N-acetylglucosaminidase (NAG) activity decreased in the implants of the groups i.p. treated with lapachol and [Bi(Lp)(2)]Cl while in the per os treatment inhibition was observed only for [Bi(Lp)(2)]Cl. Histological analysis showed that the components of the fibro-vascular tissue (vascularization and inflammatory cell population) were decreased in lapachol- and complex-treated groups. Our results suggest that both lapachol and [Bi(Lp)(2)]Cl exhibit anti-angiogenic and anti-inflammatory activities which have been attributed to the presence of the lapachol ligand. However, coordination to bismuth(III) could be an interesting strategy for improvement of lapachol's therapeutic properties.

Evaluation of the bactericidal and trypanocidal activities of triterpenes isolated from the leaves, stems, and flowers of Lychnophora pinaster

The phytochemical investigation on the aereal parts of Lychnophora pinaster Mart., Asteraceae, was carried to isolation of triterpenes. 3-O-Acetyl-lupeol (1), 3-O-acetyl-pseudotaraxasterol (2), and 3-O-acetyl-α-amyrin (3) were isolated from hexanic extract and 4,4-dimethyl-cholesta-22,24-dien-5-ol (4), α-amyrin (5), and lupeol (6) were isolated from hexanic/dichlorometanic extract of the leaves. Compounds Δ7-bauerenyl acetate (7), friedelin (8), stigmasterol (9), and sitosterol (10) were isolated from the hexanic/dichlorometanic extract of the stems. The steroids 9 and 10 were also isolated from the hexanic/dichlorometanic extract of the flowers. Triterpenes 1, 3, 4, and 7 are described for the first time in the genus Lychnophora. The apolar fractions of the leaf and stem extracts and some isolated triterpenes showed low trypanocidal activity. Moreover, apolar fractions of the leaf and stem extracts and 5 showed antibacterial action against Staphylococcus aureus.

Maytenus salicifolia Reissek, Celastraceae: triterpenes isolated from stems and antioxidant property of extracts from aerial parts

Six pentacyclic triterpenes were isolated from hexane extract of stems of Maytenus salicifolia Reissek, Celastraceae: 30-hydroxyfriedelan-3-one (1), 3,16-dioxofriedelane (2), friedeline (3), lupeol (4), betuline (5) and lup-20(29)-en-3,30-diol (6). The structure each one was established on the basis of detailed ¹H and 13C NMR spectral investigation and by comparison with the respective literature values. For compound 1, the complete 2D NMR (HMBC, HMQC and NOESY) spectral data were herein reported for the first time. Compounds 1, 2, 5 and 6 were isolated for the first time from this plant. Antioxidant activity is described for some extracts from species of the Celastraceae family, then, the extracts from aerial parts of M. salicifolia were evaluated in relation to antioxidant potential using the DPPH method. Compared to quecertin, the AcEt extract (EAF) from leaves, AcEt (EAPF) and MeOH (EMPF) from pulp fruit and AcEt (EAT) and MeOH (EMT) from stems showed significant antioxidant property.

Four Brazilian Maytenus salicifolia Reissek (Celastraceae) groups studied by TLC and UV/Vis spectrophotometry / Estudo de quatro populações de Maytenus salicifolia Reissek (Celastraceae) por CCD e espectrometria na região do UV/Vis

The great variety of angiosperms shows the need to development of botanical classification systems supported by phytochemistry, biochemistry and others. Recently, techniques of analysis used for the isolation and characterization of secondary metabolites have been employed as auxiliary quick and efficient methods for the identification and classification of plant species. M. salicifolia is popularly known in Brazil, as "small coffee" and decoct obtained from its fresh leaves is topically used to alleviate itches and other skins allergic symptoms. This work presents the use of TLC and UV/Vis spectrophotomety processes to be applied like an auxiliary method in botanical taxonomy. The results demonstrate that this process can be used in differentiation of the same genera species, and in the selection of chemical variations between individuals of the same species.

A grande variedade de angiospermas apontou a necessidade do desenvolvimento de sistemas de classificação botânica apoiada pela fitoquímica, bioquímica e outras. Recentemente, técnicas de análise utilizadas para o isolamento e caracterização de metabólitos secundários vêm sendo empregadas como métodos auxiliares rápidos e eficientes para identificação e classificação de espécies vegetais. M. salicifolia é popularmente conhecida no Brasil, como "cafezinho". O chá obtido a partir de folhas frescas é usado topicamente para aliviar pruridos e sintomas alergiformes. Este trabalho apresenta a utilização do CCD em sílica gel e espectrofotometria no UV / Vis como métodos auxiliares na identificação botânica de M. salicifolia. Os resultados demonstraram que este processo pode ser usado na diferenciação de plantas do mesmo gênero, assim como detectar variações químicas entre indivíduos de uma mesma espécie.

Evaluation of antibacterial activity of "Mangabarana" Austroplenckia populnea Reissek (Celastraceae) / Avaliação da atividade antibacteriana de "Mangabarana" Austroplenckia populnea Reissek (Celastraceae)

Austroplenckia populnea (Mangabarana) is popularly used by people from Minas Gerais, Brazil for dysenteries diseases treatment. Antitumor and antiulcer activities were also attributed to this plant. Extracts obtained using solvents of different polarities and pentacyclic triterpenes (PCTTs) isolated from these extracts through phytochemical methods were submitted to antibacterial assays. The results showed the existence of this activity and open perspectives for news studies with other organic compounds isolated from this plant.

Austroplenckia populnea (Mangabarana) é popularmente utilizada em Minas Gerais, Brasil, para o tratamento de disenterias. A ela também são atribuídas propriedades antitumoral e antiúlcera. Extratos de partes desta planta obtidos com solventes de diferentes polaridades e triterpenos pentacíclicos (TTPCs) isolados destes, por métodos fitoquímicos foram submetidos a testes de atividade antibacteriana. Os resultados mostraram a existência desta atividade e abriram perspectivas para a continuidade dos estudos com outros compostos orgânicos isolados desta planta.

Antioxidant activity of Maytenus imbricata Mart., Celastraceae / Atividade antioxidante de Maytenus imbricata Mart., Celastraceae

The free radical scavenging activity (FRS) using 2,2-diphenyl-1-picrylhydrazyl (DPPH), the reducer power and the total phenolic concentration of extracts and compounds isolated from leaves, branches and roots of Maytenus imbricata Mart. (Celastraceae) were evaluated. Some extracts, a mixture of phenolic compounds (MPC) and epicatechin showed higher RP and FRS (DPPH) activities in comparison with the standard butylhydroxyanisole (BHA) and galic acid (GA) used in assays. The ethyl acetate extract from leaves showed higher total phenolic content and also higher RP and FRS (DPPH) than the other extracts. These facts indicate that there are some relations between phenolic concentration in the extract and the antioxidant activity and the reducer power. The solvent used in the extraction process influences the chemical composition of the extracts and consequently its antioxidant and reducer power activities.

A atividade antioxidante, poder redutor (RP) e a atividade coletora de radicais livres (FRS) usando 2,2-difenil-1-picrilhidrazil (DPPH), e a concentração de substâncias fenólicas totais dos extratos e substâncias isoladas das folhas, caules e raízes de Maytenus imbricata Mart. (Celastraceae) foram avaliados. Alguns extratos, a mistura de compostos fenólicos e epicatequina mostraram alto poder redutor e atividade antioxidante (DPPH) em comparação com o padrão butilhidroxianisol (BHA) e ácido gálhico (GA) utilizados no ensaio. O extrato acetato de etila das folhas mosraram alto teor de substâncias fenólicas e alto poder redutor e atividade antioxidante em relação aos outros extratos. Este fato indica haver alguma relação entre a concentração de substâncias fenólicas e o poder redutor. O solvente usado no processo de extração influencia a composição química dos extratos e, consequentemente, as atividades redutoras e antioxidantes.