ABSTRACT
The new flavonoid (-)-4'-O-methylepicatechin 5-O-ß-D-glucopyranoside (1), along with four known triterpenes (2-5), a steroid (6), and a flavonoid (7) were isolated from the ethyl acetate extract of Maytenus quadrangulata leaves. The chemical structures of the isolated compounds were determined through analysis of 1D NMR (1H and 13C) spectroscopic data, in addition to 2D NMR and spectrometric (MS) data for compound 1. This is the first report of the isolation of daucosterol (6) and (-)-4'-O-methylepigallocatechin (7) from this species. Compounds 1 and 7 were evaluated against the bacteria Staphylococcus aureus and Klebsiella pneumoniae, but neither exhibited activity even at the highest concentration tested.
Subject(s)
Acetates , Anti-Bacterial Agents , Flavonoids , Klebsiella pneumoniae , Microbial Sensitivity Tests , Plant Extracts , Plant Leaves , Staphylococcus aureus , Triterpenes , Plant Leaves/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purification , Triterpenes/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Flavonoids/pharmacology , Staphylococcus aureus/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Klebsiella pneumoniae/drug effects , Acetates/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/chemistry , Maytenus/chemistry , Molecular StructureABSTRACT
Chagas disease and leishmaniasis are among the most widespread neglected tropical diseases, and their current therapies have limited efficacy and several toxic side effects. The present study reports the chemical and antikinetoplastid profiles of extracts from five Salvadoran Celastraceae species against the Trypanosoma cruzi epimastigotes stage and Leishmania amazonensis and Leishmania donovani promastigote forms. The phytochemical profile evinced the presence of flavonoids, tannins, sterols, and triterpenes as the main components in all plant species, whereas quinonemethide triterpenoids (QMTs) were restricted to the root bark of the studied species. Antikinetoplastid evaluation highlights the root bark extracts from Zinowewia integerrima, Maytenus segoviarum, and Quetzalia ilicina as the most promising ones, exhibiting higher potency against T. cruzi (IC50 0.71-1.58 µg/mL) and L. amazonensis (IC50 0.38-2.05 µg/mL) than the reference drugs, benznidazole (IC50 1.81 µg/mL) and miltefosine (IC50 2.64 µg/mL), respectively. This potent activity was connected with an excellent selectivity index on the murine macrophage J774A.1 cell line. These findings reinforce the potential of QMTs as antikinetoplastid agents for the development of innovative phytopharmaceuticals and the plant species under study as a source of these promising lead compounds.
ABSTRACT
Plants from Salacia genus are used in traditional medicine for a wide range of diseases. Previous studies reported bioactive pentacyclic triterpenoids from S. elliptica leaves and branches. In this study, the novel pentacyclic triterpenoid 7α,15α-dihydroxyfriedelan-3-one (1) was obtained from the roots of Salacia elliptica, along with seven known compounds: friedelan-3-one (2), friedelan-3ß-ol (3), friedelan-1,3-dione (4), friedelan-3,15-dione (5), 15α-hydroxyfriedelan-3-one (6), 15α,26-dihydroxyfriedelan-3-one (7), and 26-hydroxyfriedelan-3,15-dione (8). Additionally, one steroid, spinasterol (9), was also identified. The chemical structures of all compounds were established through 1 H and 13 C-NMR. Compound 1 was analysed by additional 2D experiments (HMBC, HSQC, COSY, and NOESY) for complete elucidation. Furthermore, the cytotoxicity of compounds 2, 3, 6, 7 and 8 against the A549 lung cancer cells model was evaluated. The flow cytometry analysis revealed a significant cytotoxic activity similar to that exhibited by the triterpenoid lupeol. Additionally, compounds 2, 3, 6, and 7 were tested for inâ vitro antifungal activity against Candida, Cryptococcus and Sporothrix strains. However, all compounds showed no activity at the tested concentrations.
ABSTRACT
The leaves of Monteverdia ilicifolia (syn. Maytenus ilicifolia), commonly called espinheira-santa, are widely used in South American traditional medicines to treat gastritis and ulcers. Several products labeled as espinheira-santa are sold as dietary supplements in retail stores and via e-commerce. Many different species with similar leaf morphology are often mistaken for Monteverdia ilicifolia and used as espinheira-santa, including Monteverdia aquifolia (Celastraceae), Citronella gongonha (Cardiopteridaceae), Jodina rhombifolia (Santalaceae), Sorocea bonplandii (Moraceae), and Zollernia ilicifolia (Fabaceae). This study aimed to characterize M. ilicifolia and distinguish it from adulterants using morphological and microscopic techniques. In addition, foreign matter and powder characteristics of botanical materials sold as "espinheira-santa" were analyzed. The morphoanatomical studies of the leaves and stems of M. ilicifolia and its five adulterant species have revealed noteworthy features that can help species identification and quality control of commercial espinheira-santa. This study showed that many commercial espinheira-santa materials were adulterated and of inferior quality.
Subject(s)
Celastraceae , Maytenus , Brazil , Microscopy , Quality Control , Plant ExtractsABSTRACT
The Celastraceae family comprises about 96 genera and more than 1.350 species, occurring mainly in tropical and subtropical regions of the world. The species of this family stand out as important plant sources of triterpenes, both in terms of abundance and structural diversity. Triterpenoids found in Celastraceae species display mainly lupane, ursane, oleanane, and friedelane skeletons, exhibiting a wide range of biological activities such as antiviral, antimicrobial, analgesic, anti-inflammatory, and cytotoxic against various tumor cell lines. This review aimed to document all triterpenes isolated from different botanical parts of species of the Celastraceae family covering 2001 to 2021. Furthermore, a compilation of their 13C-NMR data was carried out to help characterize compounds in future investigations. A total of 504 pentacyclic triterpenes were compiled and distinguished as 29 aromatic, 50 dimers, 103 friedelanes, 89 lupanes, 102 oleananes, 22 quinonemethides, 88 ursanes and 21 classified as others.
Subject(s)
Anti-Infective Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Celastraceae/chemistry , Pentacyclic Triterpenes/pharmacology , Animals , HumansABSTRACT
The expression of virulence factors, such as biofilm formation, in association with the acquisition of resistance to multiple drugs, has evidenced the need for new and effective antimicrobial agents against Staphylococcus aureus. The evaluation of the pharmacological properties of plant-derived compounds is a promising alternative to the development of new antimicrobials. In this study, we aimed to evaluate the antibacterial, antibiofilm, and the synergistic and cytotoxic effects of netzahualcoyonol isolated from Salacia multiflora (Lam.) DC. roots. Netzahualcoyonol presented bacteriostatic (1.56-25.0 µg/mL) and bactericidal (25.0-400.0 µg/mL) effects against Gram-positive bacteria, disrupted the biofilm of S. aureus, and presented a synergistic effect after its combination with ß-lactams and aminoglycosides. The low cytotoxicity of netzahualcoyonol (Selectivity Index (SI) for S. aureus (2.56), S. saprophyticus (20.56), and Bacillus subtilis (1.28)) suggests a good security profile. Taken together, these results show that netzahualcoyonol is promising for the development of a new effective antibacterial agent.
Subject(s)
Celastraceae , Salacia , Microbial Sensitivity Tests , Staphylococcus aureus , Gram-Positive Bacteria , Anti-Bacterial Agents/pharmacologyABSTRACT
Friedelin, a pentacyclic triterpene found in the leaves of the Celastraceae species, demonstrates numerous biological activities and is a precursor of quinonemethide triterpenes, which are promising antitumoral agents. Friedelin is biosynthesized from the cyclization of 2,3-oxidosqualene, involving a series of rearrangements to form a ketone by deprotonation of the hydroxylated intermediate, without the aid of an oxidoreductase enzyme. Mutagenesis studies among oxidosqualene cyclases (OSCs) have demonstrated the influence of amino acid residues on rearrangements during substrate cyclization: loss of catalytic activity, stabilization, rearrangement control or specificity changing. In the present study, friedelin synthase from Maytenus ilicifolia (Celastraceae) was expressed heterologously in Saccharomyces cerevisiae. Site-directed mutagenesis studies were performed by replacing phenylalanine with tryptophan at position 473 (Phe473Trp), methionine with serine at position 549 (Met549Ser) and leucine with phenylalanine at position 552 (Leu552Phe). Mutation Phe473Trp led to a total loss of function; mutants Met549Ser and Leu552Phe interfered with the enzyme specificity leading to enhanced friedelin production, in addition to α-amyrin and ß-amyrin. Hence, these data showed that methionine 549 and leucine 552 are important residues for the function of this synthase.
Subject(s)
Alkyl and Aryl Transferases/metabolism , Maytenus/enzymology , Plant Proteins/metabolism , Triterpenes/metabolism , Alkyl and Aryl Transferases/chemistry , Alkyl and Aryl Transferases/genetics , Amino Acid Substitution , Biosynthetic Pathways , Cyclization , Genes, Plant , Leucine/chemistry , Maytenus/genetics , Methionine/chemistry , Models, Molecular , Mutagenesis, Site-Directed , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/biosynthesis , Pentacyclic Triterpenes/metabolism , Plant Proteins/chemistry , Plant Proteins/genetics , Protein Structure, Secondary , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Substrate SpecificityABSTRACT
BACKGROUND AND AIM: Maytenus ilicifolia has analgesic, healing, antioxidant and anti-inflammatory properties. This study evaluated effect of the hydroalcoholic extract of M. ilicifolia leaves on skin wound repair. EXPERIMENTAL PROCEDURE: Wounds were induced on mice and treated with the extract. The treatment was performed daily, until day 7 after wound induction. Wound closure was measured and the features of the repaired tissue were investigated, including mast cell quantification, neutrophil and macrophage activities, collagen deposition, angiogenesis, and pro-metalloproteases and metalloproteases 2 and 9 activity (pro-MMPs and MMPs). RESULTS AND CONCLUSION: The M. ilicifolia extract accelerated the closure of wounds. The extract at a concentration of 4% was found to be effective, presenting anti-inflammatory effects and hemoglobin increased, along with increased soluble, total and type III collagens in the wound. In addition, there was an increase in pro-MMP9 and MMP9 activity after day 7th of treatment. The phenolic compounds and tannins present in this plant could be associated with the anti-inflammatory and healing activities observed in this study. Therefore, the ability to modulate essential parameters for accelerated and adequate healing as shown here suggests that the use of standardised extracts of M. ilicifolia and its fractions enriched in polyphenols may represent a therapeutic strategy for the treatment of wounds.
ABSTRACT
Cheiloclinium cognatum (Miers) A.C.Sm. is an endemic species of Brazilian Cerrado that belongs to Celastraceae family. The phytochemical study of C. cognatum branches led to the identification of ten triterpenoids (TPs), 3ß-acyloxyurs-12-ene (1), friedelin (2), ß-friedelinol (3), glut-5-en-3ß-ol (4), α-amyrin (5), ß-amyrin (6), ß-sitosterol (7), canophyllol (8), 29-hydroxyfriedelan-3-one (9) and friedelane-3ß,29-diol (10). TPs 4, 5 and 6 are described for the first Cheiloclinium genus and TPs 8 and 9 were isolated in expressive amounts. Their cytotoxic activities were evaluated against THP-1 and K562 leukemia cell lines. TPs 3 and 5 were the most active, exhibiting lower or similar IC50 against both cell lines when compared to the controls. Their mechanisms of action were investigated suggesting an intrinsic mitochondrial pathway of apoptosis evidenced by up-regulation of BAK mRNA expression. Chemometric studies indicated that their activities may be related to their molecular size and shape as well as electronic interactions of C-3 hydroxy group with molecular targets.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Celastraceae/chemistry , Leukemia/pathology , Triterpenes/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Triterpenes/isolation & purificationABSTRACT
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.
Subject(s)
Celastraceae/chemistry , Oils, Volatile/analysis , Brazil , Gas Chromatography-Mass Spectrometry , Principal Component Analysis , Species SpecificityABSTRACT
Medium and high polarity extracts from Maytenus species are known to contain polyphenolic compounds such as proanthocyanidins. The high polarity and structural complexity of these compounds make very difficult their isolation even by modern chromatographic techniques. Maytenus cajalbanica (Borhidi & O. Muñiz) Borhidi & O. Muñiz is endemic from Cuba. So far, there are reports neither of phytochemical work nor of biological evaluation of extracts from this subspecies. The goal of this work is to determine the polyphenolic profile and the antioxidant capacity of the ethanolic extract from the barks of Maytenus cajalbanica. FIA/ESI/IT/MSn analysis allowed the identification of 5 flavan-3-ol monomers, 33 proanthocyanidins, 2 free flavonoids and their respective glycosides as major compounds of the ethanolic extract, which showed a strong radical scavenging capacity and a significant ferric reduction power. FIA/ESI/IT/MSn technique led the rapid, effective and sensitive determination of the polyphenolic profile of Maytenus cajalbanica without previous separation.
Subject(s)
Antioxidants/pharmacology , Maytenus/chemistry , Plant Extracts/pharmacology , Polyphenols/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Antioxidants/chemistry , Biphenyl Compounds/chemistry , Ethanol/chemistry , Flavonoids/analysis , Glycosides/analysis , Picrates/chemistry , Plant Bark/chemistry , Plant Extracts/chemistry , Polyphenols/chemistry , Proanthocyanidins/analysisABSTRACT
Peritassa campestris (Celastraceae) root bark accumulates potent antitumor quinonemethide triterpenes (QMTs). When grown in their natural habitat, plants of the family Celastraceae produce different QMTs such as celastrol (3) and pristimerin (4). However, when they are inserted in in vitro culture systems, they accumulate maytenin (1) as the main compound. Recently, Bacillus megaterium was detected as an endophytic microorganism (EM) living inside P. campestris roots cultured in vitro. We hypothesized that compound (1) controls EM growth more efficiently, and that the presence of EMs in the root culture causes compound (1) to accumulate. For the first time, this work has explored plant-microorganism interaction in a species of the family Celastraceae by co-culture with an EM. Live endophytic bacteria were used, and QMT accumulation in P. campestris adventitious roots was our main focus. The antimicrobial activity of the main QMTs against endophytic B. megaterium was also evaluated. Our results showed that compound (1) and maytenol (5) were more effective than their precursors QMTs (3) and (4) in controlling the EM. Co-culture of B. megaterium with roots significantly reduced bacterial growth whereas root development remained unaffected. Compound (1) production was 24 times higher after 48 hr in the presence of the highest B. megaterium concentration as compared to the control. Therefore, P. campestris adventitious roots affect the development of the endophyte B. megaterium through production of QMTs, which in turn can modulate production of compound (1).
Subject(s)
Bacillus megaterium/metabolism , Celastraceae/metabolism , Plant Extracts/chemistry , Plant Roots/metabolism , Triterpenes/chemistry , Anti-Infective Agents/chemistry , Antineoplastic Agents/chemistry , Endophytes/metabolism , Pentacyclic Triterpenes , Time FactorsABSTRACT
ABSTRACT Objective: In the present study, five new source compounds isolated from aerial parts of Gymnosporia royleana (G royleana) were screened for antibacterial and antifungal activities. Methods: Extraction from plant material was carried out using cold maceration technique. Isolation of pure compounds was accomplished through repeated column chromatography of different fractions obtained from crude extract and using silica gel as stationary phase. Their structures were established via advanced spectroscopic techniques along with the spectral data previously reported for these compounds. Dilution method was used for the evaluation of antimicrobial potential of the compounds against various microbial strains. Results: Among the tested compounds, Gymnosporin B displayed moderate antimicrobial activity against Escherichia Coli (E coli), Staphylococcus aureus (S aureus), Candida albicans (C albicans) and Aspergillus flavus (A flavus) [minimum inhibitory concentration (MIC) range; 32-64 μg/mL]. Similarly, Gymnosporin C also showed moderate activity against E coli and S aureus (MIC; 32 μg/mL each) as well as weak activity against C albicans and A flavus (MIC; 64 μg/mL each). However, Royaflavone showed moderate antibacterial activity against S aureus only (MIC; 32 μg/mL). Antimicrobial activity of the rest of the compounds was weak and negligible. Conclusion: The present study has provided fascinating results of antimicrobial activities of the isolated compounds. However, the broad antimicrobial spectrum of Gymnosporin B and Gymnosporin C demands for further exploration of these triterpenes, both on the basis of mechanism and quantitative structure-activity relationship.
RESUMEN Objetivo: En el presente estudio, cinco nuevos compuestos de origen aislados de partes aéreas de Gymnosporia royleana (G royleana) fueron tamizados en sus actividades antibacterianas y antifúngicas. Métodos: La extracción de material vegetal se realizó mediante la técnica de maceración en frío. El aislamiento de compuestos puros se logró a través de la cromatografía en columna repetida de diversas fracciones obtenidas del extracto crudo y usando gel de silicona como fase estacionaria. Sus estructuras fueron establecidas mediante técnicas espectroscópicas avanzadas junto con los datos espectrales previamente reportados para estos compuestos. El método de dilución fue usado para evaluar el potencial antimicrobiano de los compuestos contra diversas cepas microbianas. Resultados: Entre los compuestos sometidos a prueba, Gymnosporina B mostró una actividad antimicrobiana moderada contra Escherichia Coli (E coli), Staphylococcus aureus (S aureus), Candida Albicans (C albicans) y Aspergillus flavus (A flavus) [rango de concentración inhibitoria mínima (CIM); 32 - 64 μg/mL]. De manera similar, Gymnosporina C también mostró actividad moderada contra E coli y S aureus (CIM; 32 μg/mL cada uno) así como débil actividad frente a C albicans y A flavus (CIM; 64 μg/mL cada uno). Sin embargo, Royaflavone mostró actividad antibacteriana moderada sólo frente a S aureus (CIM; 32 μg/mL). La actividad antimicrobiana del resto de los compuestos fue débil e insignificante. Conclusión: El presente estudio ha proporcionado resultados interesantes acerca de las actividades antimicrobianas de los compuestos aislados. Sin embargo, el amplio espectro antimicrobiano de la Gymnosporina B y la Gymnosporina C exige una mayor exploración de estos triterpenos, tanto sobre la base del mecanismo como a partir de la relación cuantitativa estructura-actividad.
Subject(s)
Plant Extracts/isolation & purification , Phytotherapy , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Ascomycota/drug effects , Aspergillus flavus/drug effects , Candida albicans/drug effects , Plant Extracts/pharmacology , Celastraceae/chemistry , Gram-Negative Bacteria , Gram-Positive Bacteria/drug effectsABSTRACT
Mayaro virus (MAYV) is a sublethal arbovirus transmitted by mosquitoes with possible installation of an urban cycle in the Americas. Its infection causes disabling arthralgia, and still, there is no vaccine or treatment to it. We recently investigated nearly 600 compounds by molecular docking and identified epicatechin as a potent antiviral against MAYV. The root extract of Maytenus imbricata showed anti-MAYV activity and two isolated compounds from this plant were also evaluated in vitro. Proanthocyanidin (PAC), a dimer containing epicatechin, showed an effective concentration for 50% of the cells infected by MAYV (EC50) of 37.9⯱â¯2.4⯵M and a selectivity index (SI) above 40. PAC showed significant virucidal activity, inhibiting 100% of the virus proliferation (7 log units), and caused moderate effect during adsorption and virus internalization stage. However, PAC was unable to block the infection when only the cells were pretreated. It was observed a reduction in virus yields when adding PAC at different moments after infection. The set of results indicates that PAC binds to viral and non-cellular elements and may inactivate the MAYV. The inactivation occurs before infection or when the virus reaches the extracellular environment from the 2nd cycle of infection that could block its progression cell-to-cell or to tissues not yet infected.
Subject(s)
Alphavirus/drug effects , Antiviral Agents/pharmacology , Proanthocyanidins/pharmacology , Alphavirus Infections/virology , Animals , Antiviral Agents/chemistry , Catechin/chemistry , Catechin/pharmacology , Cell Survival/drug effects , Chlorocebus aethiops , Magnoliopsida/chemistry , Molecular Structure , Plant Roots/chemistry , Proanthocyanidins/chemistry , Vero Cells , Virus Attachment/drug effects , Virus Internalization/drug effects , Virus Replication/drug effectsABSTRACT
Biodiversity is key for maintenance of life and source of richness. Nevertheless, concepts such as phenotype expression are also pivotal to understand how chemical diversity varies in a living organism. Sesquiterpene pyridine alkaloids (SPAs) and quinonemethide triterpenes (QMTs) accumulate in root bark of Celastraceae plants. However, despite their known bioactive traits, there is still a lack of evidence regarding their ecological functions. Our present contribution combines analytical tools to study clones and individuals of Maytenus ilicifolia (Celastraceae) kept alive in an ex situ collection and determine whether or not these two major biosynthetic pathways could be switched on simultaneously. The relative concentration of the QMTs maytenin (1) and pristimerin (2), and the SPA aquifoliunin E1 (3) were tracked in raw extracts by HPLC-DAD and ¹H-NMR. Hierarchical Clustering Analysis (HCA) was used to group individuals according their ability to accumulate these metabolites. Semi-quantitative analysis showed an extensive occurrence of QMT in most individuals, whereas SPA was only detected in minor abundance in five samples. Contrary to QMTs, SPAs did not accumulate extensively, contradicting the hypothesis of two different biosynthetic pathways operating simultaneously. Moreover, the production of QMT varied significantly among samples of the same ex situ collection, suggesting that the terpene contents in root bark extracts were not dependent on abiotic effects. HCA results showed that QMT occurrence was high regardless of the plant age. This data disproves the hypothesis that QMT biosynthesis was age-dependent. Furthermore, clustering analysis did not group clones nor same-age samples together, which might reinforce the hypothesis over gene regulation of the biosynthesis pathways. Indeed, plants from the ex situ collection produced bioactive compounds in a singular manner, which postulates that rhizosphere environment could offer ecological triggers for phenotypical plasticity.
Subject(s)
Maytenus/chemistry , Plant Extracts/chemistry , Spermidine/analogs & derivatives , Triterpenes/chemistry , Alkaloids/chemistry , Alkaloids/isolation & purification , Cells, Cultured , Chromatography, High Pressure Liquid , Ecology , Humans , Pentacyclic Triterpenes , Plant Bark/chemistry , Plant Roots/chemistry , Pyridines/chemistry , Pyridines/isolation & purification , Quinones/chemistry , Quinones/isolation & purification , Rhizosphere , Spermidine/chemistry , Spermidine/isolation & purification , Triterpenes/isolation & purificationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Salacia impressifolia (Miers) A. C. Smith (family Celastraceae) is a traditional medicinal plant found in the Amazon Rainforest known as "miraruíra", "cipó-miraruíra" or "panu" and is traditionally used to treat dengue, flu, inflammation, pain, diabetes, male impotency, renal affections, rheumatism and cancer. AIM OF THE STUDY: The aim of this study was to investigate in vitro and in vivo anti-leukemia activity of the stem bark of S. impressifolia in experimental models. MATERIALS AND METHODS: The in vitro cytotoxic activity of extracts, fractions and quinonemethide triterpenes (22-hydroxytingenone, tingenone and pristimerin) from the stem bark of S. impressifolia in cultured cancer cells was determined. The in vivo antitumor activity of the ethyl acetate extract (EAE) and of its fraction (FEAE.3) from the stem bark of S. impressifolia was assessed in C.B-17 severe combined immunodeficient (SCID) mice engrafted with human promyelocytic leukemia HL-60 cells. RESULTS: The extract EAE, its fraction FEAE.3, and quinonemethide triterpenes exhibited potent cytotoxicity against cancer cell lines, including in vitro anti-leukemia activity against HL-60 and K-562 cells. Moreover, extract EAE and its fraction FEAE.3 inhibited the in vivo development of HL-60 cells engrafted in C.B-17 SCID mice. Tumor mass inhibition rates were measured as 40.4% and 81.5% for the extract EAE (20â¯mg/kg) and for its fraction FEAE.3 (20â¯mg/kg), respectively. CONCLUSIONS: Ethyl acetate extract and its fraction from the stem bark of S. impressifolia exhibit in vitro and in vivo anti-leukemia activity that can be attributed to their quinonemethide triterpenes. These data confirm the ethnopharmacological use of this species and may contribute to the development of a novel anticancer herbal medicine.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Leukemia/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Salacia , Animals , Cell Line , Female , Humans , Leukemia/pathology , Mice, SCID , Phytotherapy , Plant Bark , Plant StemsABSTRACT
The new pentacyclic triterpene 11ß-hydroxypristimerin (1), along with the known metabolites pristimerin (2), 6-oxopristimerol (3) and vitideasin (4), were isolated from a Salacia crassifolia root wood extract, following a bioassay-guided fractionation approach. Both the extract and the purified triterpenes displayed pronounced cytotoxic activity against human cancer cell lines. The NCI-60 cell line screen revealed that compound 2 was the most active, with a mean GI50 of 0.17 µM, while compound 1 had a mean GI50 of 8.7 µM. A COMPARE analysis of the screening results showed that pristimerin is likely to be the main compound responsible for the cytotoxic activity of the extract (mean GI50 of 0.3 µg·mL−1). A targeted search for pristimerin and related derivatives using LC-MS/MS revealed the presence of pristimerin (2) and 6-oxopristimerol (3) in all Celastraceae species examined and in all plant parts tested, while vitideasin (4) was only detected in the genus Salacia.
Subject(s)
Celastraceae/metabolism , Metabolomics/methods , Plant Extracts/chemistry , Salacia/chemistry , Triterpenes/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/metabolism , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Humans , Pentacyclic Triterpenes , Plant Roots/chemistry , Structure-Activity Relationship , Triterpenes/isolation & purification , Triterpenes/metabolism , Triterpenes/therapeutic useABSTRACT
As part of a project studying the secondary metabolites extracted from the Chilean flora, we report herein three new ß-agarofuran sesquiterpenes, namely (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), C27H32O11, (II), (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-5,10-diyl bis(furan-3-carboxylate), C27H32O10, (III), and (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, C29H34O9, (IV), obtained from the seeds of Maytenus boaria and closely associated with a recently published relative [Paz et al. (2017). Acta Cryst. C73, 451-457]. In the (isomorphic) structures of (II) and (III), the central decalin system is esterified with an acetate group at site 1 and furoate groups at sites 6 and 9, and differ at site 8, with an OH group in (II) and no substituent in (III). This position is also unsubstituted in (IV), with site 6 being occupied by a benzoate group. The chirality of the skeletons is described as 1S,4S,5S,6R,7R,8R,9R,10S in (II) and 1S,4S,5S,6R,7R,9S,10S in (III) and (IV), matching the chirality suggested by NMR studies. This difference in the chirality sequence among the title structures (in spite of the fact that the three skeletons are absolutely isostructural) is due to the differences in the environment of site 8, i.e. OH in (II) and H in (III) and (IV). This diversity in substitution, in turn, is responsible for the differences in the hydrogen-bonding schemes, which is discussed.
Subject(s)
Furans/chemistry , Maytenus/chemistry , Sesquiterpenes/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Magnetic Resonance Spectroscopy , Seeds , Sesquiterpenes/isolation & purification , StereoisomerismABSTRACT
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.
Subject(s)
Antiviral Agents/pharmacology , Plant Extracts/pharmacology , Maytenus/chemistry , Dengue Virus/drug effects , Pentacyclic Triterpenes/pharmacology , Anti-Bacterial Agents/pharmacology , Antidiarrheals/pharmacology , Antiviral Agents/isolation & purification , Cell Line , Maytenus/classification , Pentacyclic Triterpenes/isolation & purification , Anti-Bacterial Agents/isolation & purification , Antidiarrheals/isolation & purificationABSTRACT
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.