RESUMEN

The decoction of Salvia lachnostachys Benth. leaves is used in Brazilian folk medicine for anti-spasmodic, antipyretic, and anxiolytic purposes. Some of the biological effects of an S. lachnostachys extract have been shown to be anti-inflammatory, anti-cancer, and antidepressant effects. In addition, this medicinal plant produces several compounds including icetexane diterpenoids, such as fruticuline A and fruticuline B. The aim of the present work was to evaluate the anti-hyperalgesic and anti-inflammatory properties of fruticuline B (FRUT B) and the ethanolic extract obtained from the leaves of S. lachnostachys (EESL) in experimental mouse models. EESL (30, 100, and 300 mg/kg) and FRUT B (1 mg/kg) were evaluated in articular inflammation-induced models in Swiss mice. In articular inflammation induced by Zymosan, EESL (300 mg/kg) and FRUT B (1 mg/kg) significantly reduced mechanical hyperalgesia (83.17% inhibition for EESL and 81.19% for FRUT B); edema (68.75% reduction for EESL and 33.66% for FRUT B); leukocyte migration (81.3% for EESSL and 92.2% for FRUT B), and nitric oxide production (88.3% for EESL and 74.4% for FRUT B). The exposure to fruticuline B significantly inhibited the edema (51.5%), mechanical (88.12%) and cold hyperalgesia (80.8%), and myeloperoxidase (MPO) (63.4%) activity 24 h after CFA injection. In the pleurisy model, FRUT B reduced 89.1% of leukocyte migration and 50.3% in nitric oxide production. Four hours after carrageenan injection, FRUT B (1 mg/kg) diminished 89.11% of mechanical hyperalgesia, 65.8% of paw edema, and 82.12% of the response to cold hyperalgesia. In the MTT test, EESL and fruticuline B caused no cytotoxicity. The present study revealed, for the first time, the anti-arthritic and anti-nociceptive effects of FRUT B, pointing out the therapeutic potential of the species to control inflammation and nociception. Future studies are needed to evaluate other biological properties of fruticuline B and to better understand its mechanism of action.

RESUMEN

Azorella compacta (A. compacta) is a shrub of the Andean Altiplano of Bolivia, Chile and Peru, consumed by local communities as a traditional medicine for several maladies such as diabetes, hepatic and inflammatory diseases. A. compacta is rich in mulinane- and azorellane-type diterpenoids. For two of these, acute hypoglycemic effects have been described, but the impact of A. compacta diterpenoids on fatty liver disease has not been investigated. Therefore, A. compacta organic fractions were prepared using petroleum ether, dichloromethane and methanol. Their content was characterized by UHPLC/MS, revealing the presence of ten diterpenoids, mainly mulinic acid, azorellanol and mulin-11,13-diene. Next, mice fed with a high-fat diet (HFD), a model of metabolic dysfunction-associated fatty liver disease (MAFLD), received one of the fractions in drinking water for two weeks. After this treatment, hepatic parameters were evaluated. The A. compacta fractions did not reduce hyperglycemia or body weight in the HFD-fed mice but increased the serum levels of hepatic transaminases (AST and ALT), reduced albumin and increased bilirubin, indicating hepatic damage, while histopathological alterations such as steatosis, inflammation and necrosis generated by the HFD were, overall, not ameliorated by the fractions. These results suggest that organic A. compacta extracts may generate hepatic complications in patients with MAFLD.

RESUMEN

From the aerial parts of Salvia carranzae Zamudio and Bedolla, three new icetexane-type diterpenoids were isolated. Their structures were established through spectroscopic methods and named the following: salvicarranzanolide (1), 19-deoxo-salvicarranzanolide (2) and 19-deoxo-20-deoxy-salvicarranzanolide (3). In addition, the known icetexane-type diterpenoids, 6,7,11,14-tetrahydro-7-oxo-icetexone (4), iso-icetexone (5), 19-deoxo-iso-icetexone (6), icetexone (7), 19-deoxo-icetexone (8) and 7α-acetoxy-6,7-dihydroicetexone (9), were also isolated, along with the abietanes sessein (10) and ferruginol (11). α-Tocopherol was also identified. Compounds 5, 6 and 8 were tested for their antiproliferative activity using the sulforhodamine B assay on six cancer and one normal human cell lines. Diterpenoids 5 and 6 showed noteworthy antiproliferative activity, exhibiting an IC50 (µM) = 0.43 ± 0.01 and 1.34 ± 0.04, respectively, for U251 (glioblastoma), an IC50 (µM) = 0.45 ± 0.01 and 1.29 ± 0.06 for K5621 (myelogenous leukemia), 0.84 ± 0.07 and 1.03 ± 0.10 for HCT-15 (colon cancer), and 0.73 ± 0.06 and 0.95 ± 0.09 for SKLU-1 (lung adenocarcinoma) cell lines. On the other hand, the phytotoxicity of compounds 5-7 and 9-10 was evaluated on seed germination and root growth in some weeds such as Medicago sativa, Panicum miliaceum, Amaranthus hypochondriacus and Trifolium pratense as models. While compounds 5 and 10 exhibited a moderate inhibitory effect on the root growth of A. hypochondriacus and T. pratense at 100 ppm, the diterpenoids 6, 7 and 9 were ineffective in all the plant models. Taxonomic positions based on the chemical profiles found are also discussed.

Asunto(s)

Alcaloides , Diterpenos , Neoplasias Pulmonares , Salvia , Humanos , Abietanos/farmacología , Abietanos/química , Salvia/química , Diterpenos/farmacología , Diterpenos/química , Línea Celular Tumoral , Estructura Molecular

RESUMEN

The present study shows the untargeted metabolite profiling and in vitro antibacterial, cytotoxic, and nitric oxide (NO) inhibitory activities of the methanolic leaves extract (MLE) and methanolic stem extract (MSE) of Erythroxylum mexicanum, as well as the fractions from MSE. Using ultra-high performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS), a total of 70 metabolites were identified; mainly alkaloids in the MLE, while the MSE showed a high abundance of diterpenoids. The MSE fractions exhibited differential activity against Gram-positive bacteria. Notably, the hexane fraction (HSF) against Streptococcus pyogenes ATCC 19615 (MIC=62.5 µg/mL) exhibited a bactericidal effect. The MSE fractions exhibited cytotoxicity against all cancer cell lines tested, with selectivity towards them compared to a noncancerous cell line. Particularly, the HSF and chloroform fraction (CSF) showed the highest cytotoxicity against prostate cancer (PC-3) cells, with IC50 values of 19.9 and 18.1 µg/mL and selectivity indexes of 3.8 and 4.2, respectively. Both the HSF and ethyl acetate (EASF) fractions of the MSE inhibited NO production in RAW 264.7 macrophages, with NO production percentages of 50.0 % and 51.7 %, respectively, at a concentration of 30 µg/mL. These results indicated that E. mexicanum can be a source of antibacterial, cytotoxic, and anti-inflammatory metabolites.

Asunto(s)

Antineoplásicos , Espectrometría de Masas en Tándem , Masculino , Humanos , Óxido Nítrico , Extractos Vegetales/química , Cromatografía Líquida de Alta Presión , Antibacterianos/farmacología , Antineoplásicos/farmacología , Metanol/química

RESUMEN

Four novel seconeodolastane diterpenoids, named tricholomalides D-G, were isolated, together with the known tricholomalide C, from the fruiting bodies of Tricholoma ustaloides Romagn., a species belonging to the large Tricholoma genus of higher mushrooms (Basidiomycota, family Tricholomataceae). They were isolated through multiple chromatographic separations, and the structures, including the absolute configuration, were established through a detailed analysis of MS, NMR, and CD spectral data and comparison with related compounds reported in the literature, which has been thoroughly revised.

Asunto(s)

Fagus , Tricholoma , Madera , Tricholoma/química , Espectroscopía de Resonancia Magnética

RESUMEN

BACKGROUND: Kaurane-type diterpenoids, obtained from various natural sources, have shown many biological activities, including anti-inflammatory and antitumor effects. Caracasine, an ent-kaurane diterpenoid isolated from the flowers of Croton micans, was shown to induce apoptosis in leukaemia cell lines. OBJECTIVE: The present study aimed to ascertain the compound's mechanism of cell death induction using two leukaemia cell lines, Jurkat E6.1 (T cell) and HL-60 (promyeloblast cells). METHODS: Cell death in Jurkat and HL60 cells were evaluated by flow cytometry for apoptosis with annexin-V/PI, mitochondrial membrane potential disturbance, changes in cell cycle, CD95 expression, caspase activation, Nuclear Factor kappa B inhibition, and differentiation into a neutrophil-like cell (dHL60). RESULTS: Caracasine (10 µM) increased the G0/G1 phase in Jurkat and arrested the cell cycle in the S phase in HL60. Caracasine increased CD95 expression (p<0.01 in Jurkat and p<0.05 in HL60) and caspase-8 activation (p<0.001 in Jurkat and p<0.05 in HL60). Caspase-9 was activated in both cell lines (p<0.001) along with the decline in mitochondrial Δψm (p<0.05 in Jurkat and p<0.001 in HL60). In HL60 cells, the kaurane induced neutrophil differentiation was assessed by CD40 expression and reactive oxygen species production. In Jurkat cells, caracasine inhibited the NF-κB pathway in cells pretreated with PHA to activate the NF-κB pathway, suggesting a possible role in inflammatory diseases. CONCLUSION: Caracasine induced apoptosis through the intrinsic and extrinsic pathways in both cell lines were evaluated which could be the leading structure for new anti-leukemic and anti-inflammatory drugs.

Asunto(s)

Diterpenos de Tipo Kaurano , Diterpenos , Leucemia , Humanos , Diterpenos de Tipo Kaurano/farmacología , Diterpenos de Tipo Kaurano/química , FN-kappa B/metabolismo , Diterpenos/farmacología , Apoptosis , Células HL-60 , Leucemia/tratamiento farmacológico , Células Jurkat

RESUMEN

Three new diterpenoids, demethylfruticuline B (1), 20-hydroxyfruticuline B (2), and 6-hydroxyisofruticuline A (3) were isolated from the leaves of Salvia lachnostachys Benth, together with five known compounds: fruticuline B (4), fruticuline A (5), demethylfruticuline A (6), heterobetulinic acid (7), and maslinic acid (8). The known compounds 7-8 are being reported for the first time in this species. Compounds 1 and 4-6 were tested for antioxidant activity using the ORAC-FL method, and the antioxidant capacity was measured as relative trolox equivalent. All compounds were active, with values of relative trolox equivalent varying between 1.20-2.42. The most active compound was demethylfruticuline B (1).

Asunto(s)

Diterpenos , Salvia , Hojas de la Planta , Extractos Vegetales , Antioxidantes/farmacología , Estructura Molecular

RESUMEN

Malaria is a parasitic disease caused by protozoan parasites from the genus Plasmodium. Plasmodium falciparum is the most prevalent species worldwide and the causative agent of severe malaria. The spread of resistance to the currently available antimalarial therapy is a major concern. Therefore, it is imperative to discover and develop new antimalarial drugs, which not only treat the disease but also control the emerging resistance. Brussonol is an icetexane derivative and a member of a family of diterpenoids that have been isolated from several terrestrial plants. Here, the synthesis and antiplasmodial profiling of a series of brussonol derivatives are reported. The compounds showed inhibitory activities in the low micromolar range against a panel of sensitive and resistant P. falciparum strains (IC50s = 5-16 µM). Moreover, brussonol showed fast-acting in vitro inhibition and an additive inhibitory behavior when combined with the antimalarial artesunate (FICindex~1). The mode of action investigation indicated that brussonol increased the cytosolic calcium levels within the parasite. Hence, the discovery of brussonol as a new scaffold endowed with antiplasmodial activity will enable us to design derivatives with improved properties to deliver new lead candidates for malaria.

RESUMEN

This study presents the cytotoxic activity evaluation of the natural diterpenes ent-kaurenoic acid (1) and its 15ß-hydroxy (2), 15ß-senecioyloxy (3), and 15ß-tiglinoyloxy (4) derivatives, isolated from Brazilian native plants, Baccharis retusa and B. lateralis (Asteraceae). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay, it was observed that compound 1 displayed in vitro activity towards the aggressive MDA-MB-231 adenocarcinoma cell line and reduced toxicity against MCF-10A nontumorigenic epithelial cells, indicating expressive selectivity. On the contrary, compounds 2-4 exhibited reduced toxicity and selectivity in both tested cell lines. Based on the chemical structures of compounds 1-4, it is suggested that the presence of additional functional groups at the C-15 position-a hydroxyl group in compound 2 and isomeric isoprene units in compounds 3 and 4-might be responsible for the reduction in the potential/selectivity. In silico studies show, for compounds 1-4, good predictions regarding bioavailability and ADME (absorption, distribution, metabolism, and excretion) properties as well as no alerts for PAINS (pan-assay structures interference). In conclusion, ent-kaurenoic acid (1), a common diterpenoid isolated in high amounts from different plants belonging to the Baccharis genus, has been shown to be a promising cytotoxic agent against an aggressive adenocarcinoma cell line (MDA-MB-23) and, if well exploited, could be used as a scaffold in the development of molecular prototypes for the treatment of breast cancer.

Asunto(s)

Adenocarcinoma , Antineoplásicos , Baccharis , Diterpenos de Tipo Kaurano , Diterpenos , Antineoplásicos/química , Baccharis/química , Diterpenos/farmacología , Diterpenos de Tipo Kaurano/química , Humanos , Relación Estructura-Actividad

RESUMEN

The funerary rites of particular members of the pre-Hispanic Mayan society included the pigmentation of the corpse with a red color. In order to understand this ritual, it is first necessary to identify the constituents of the pigment mixture and then, based on its properties, analyze the possible form and moment of application. In the present approach, 1H-NMR analysis was carried to detect organic components in the funerary pigments of Xcambó, a small Maya settlement in the Yucatan Peninsula. The comparison of the spectra belonging to the pigment found in the bone remains of seven individuals, and those from natural materials, led to the identification of beeswax and an abietane resin as constituents of the pigment, thus conferring it agglutinant and aromatic properties, respectively. The 1H-NMR analysis also allowed to rule out the presence of copal, a resin found in the pigment cover from paramount chiefs from the Mayan society. Additionally, a protocol for the extraction of the organic fraction from the bone segment without visible signs of analysis was developed, thus broadening the techniques available to investigate these valuable samples.

RESUMEN

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the Azorella, Laretia, and Mulinum genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives. This systematic review highlights the biosynthetic origin, the chemistry, and the pharmacological activities of this remarkably interesting group of diterpenoids.

Asunto(s)

Apiaceae/química , Diterpenos/química , Plantas Medicinales/química , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Diterpenos/síntesis química , Diterpenos/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/farmacología

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Croton floribundus Spreng. (Euphorbiaceae), popularly known as Capixinguí, stands out due to its widespread use in traditional medicine to treat wounds, syphilis, hemorrhoids, eye diseases and as a purgative. AIM OF THE STUDY: To characterize clerodanes diterpenes from C. floribundus and to evaluate the effects of the fraction and diterpenes (1-5) on inhibition of nitrite production. MATERIALS AND METHODS: The hydroethanolic root extract of C. floribundus was fractionated on a solid phase extraction column to obtain the fraction named Fr80%. From this, five compounds were obtained and characterized. The absolute configuration of compound 1 was determined by a combination of electronic and vibrational circular dichroism spectroscopies. Additionally, compounds 1-5 were evaluated for their inhibitory effects on nitrite production induced by lipopolysaccharide (LPS) in RAW 264 macrophage cell. RESULTS: Five clerodane diterpenoids were characterized, and the absolute stereochemistry of 1 was established as 3R,4R,5R,8R,9R,10S,12S. The IC50 values obtained through inhibition of nitrite production were 28.52 ±â€¯2.21 µM (1), 40.26 ±â€¯2.79 µM (2), 25.47 ±â€¯2.16 µM (3), 35.78 ±â€¯2.93 µM (4) and 40.58 ±â€¯4.78 µM (5). In the tested concentrations, the samples presented low toxicity in macrophages. CONCLUSIONS: Four new diterpenes were characterized from C. floribundus, these being croflorins A-D (1-4) and a known halimane (5). These compounds exhibited inhibitory effect on nitrite production.

Asunto(s)

Croton/química , Diterpenos/química , Diterpenos/farmacología , Nitritos/metabolismo , Animales , Línea Celular , Dicroismo Circular/métodos , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Euphorbiaceae/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Medicina Tradicional/métodos , Ratones , Células RAW 264.7

RESUMEN

For the first time, the pigment composition of basidiocarps from the Chilean mushroom Cortinarius pyromyxa was studied under various aspects like phylogeny, chemistry and antibiotic activity. A molecular biological study supports the monotypic position of C. pyromyxa in subgenus Myxacium, genus Cortinarius. Four undescribed diterpenoids, named pyromyxones A-D, were isolated from fruiting bodies of C. pyromyxa. Their chemical structures were elucidated based on comprehensive one- and two-dimensional NMR spectroscopic analysis, ESI-HRMS measurements, as well as X-ray crystallography. In addition, the absolute configurations of pyromyxones A-D were established with the aid of JH,H, NOESY spectra and quantum chemical CD calculation. The pyromyxones A-D possess the undescribed nor-guanacastane skeleton. Tested pyromyxones A, B, and D exhibit only weak activity against gram-positive Bacillus subtilis and gram-negative Aliivibrio fischeri as well as the phytopathogenic fungi Botrytis cinerea, Septoria tritici and Phytophthora infestans.

Asunto(s)

Antibacterianos/farmacología , Cortinarius/química , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Pigmentos Biológicos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Cristalografía por Rayos X , Diterpenos/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Filogenia , Pigmentos Biológicos/química , Pigmentos Biológicos/aislamiento & purificación , Teoría Cuántica

RESUMEN

Mulinum crassifolium Phil. (Apiaceae) is an endemic shrub from Chile commonly used as infusion in traditional medicine to treat diabetes, bronchial and intestinal disorders and stomach ailments, including ulcers. From the EtOAc extract of this plant, the new mulinane-type diterpenoids 3 and 5 were isolated along with three known diterpenoids. The gastroprotective effect of the infusion of the plant was assayed to support the traditional use and a fast HPLC analysis using high resolution techniques was performed to identify the bioactive constituents. The EtOAc extract and the edible infusion showed gastroprotective effect at 100 mg/kg in the HCl/EtOH induced gastric ulcer model in mice, reducing lesions by 33% and 74%, respectively. Finally, a metabolomic profiling based on UHPLC-ESI-MS/HRMS of the edible infusion was performed and thirty-five compounds were tentatively identified including quercetin, caffeic acid, apigenine glucoside, p-coumaric acid, chlorogenic acids, and caffeoylquinic acids, which have been associated previously with gastroprotective and antiulcer properties. This scientific evidence can support the contribution of polyphenols in the gastroprotective activity of the edible infusion of this plant, and can validate at least in part, its ethnopharmacological use.

Asunto(s)

Apiaceae/química , Cromatografía Líquida de Alta Presión , Diterpenos/química , Diterpenos/farmacología , Tracto Gastrointestinal/efectos de los fármacos , Espectrometría de Masas , Extractos Vegetales/química , Animales , Metaboloma , Metabolómica , Ratones , Estructura Molecular

RESUMEN

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Asunto(s)

Asteraceae/química , Diterpenos/química , Antiinfecciosos/química , Antiinfecciosos/aislamiento & purificación , Antiinfecciosos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antioxidantes/química , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Asteraceae/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cristalografía por Rayos X , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Hongos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Leishmania/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Conformación Molecular , Extractos Vegetales/química

RESUMEN

Abstract In this study, sahandone (1) and a new diterpenoid named sahandol II (2) were isolated from the roots of Salvia chloroleuca Rech. f. & Aellen, Lamiaceae. The absolute configurations of compounds 1 and 2 were assigned by comparison of experimental electronic circular dichroism spectra and comparing with published data. Cytotoxic and apoptotic evaluation of the isolated compounds and the methanol crude extract and its subfractions including petroleum ether, dichloromethane, ethyl acetate, n-butanol and aqueous fraction on two human prostate cancer cell lines and a breast cancer cell lines, showed that non-polar and semi-polar subfractions had the potent cytotoxic effect on PC3 cells with the IC50 values of 24.19, 33.59, and 47.15 µg/ml, respectively. Sub-G1 peak in flow cytometry histogram of cells treated with petroleum ether, dichloromethane and ethyl acetate subfractions showed the induction of apoptosis. Change in the Bax/Bcl-2 ratio and cleavage of poly ADP-ribose polymerase were observed.

RESUMEN

Abstract The chemical study of roots from Azadirachta indica A. Juss., Meliaceae, led to the isolation of two new terpenoids, limonoid morenolide and diterpene 17-hydroxy-sandaracopimar-8,15-dien-11-one, in addition to the four well-known limonoids nimbinene, nimbinal, nimbandiol and salannin, and three diterpenoids nimbidiol, ferruginol, and 6,7-dehydroferruginol. Their structural elucidations were based on one and bidimensional Nuclear Magnetic Resonance and Electrospray ionization mass spectrometry spectra data which was compared to the data found in literature. The anti-inflammatory, cytotoxic and antimycobacterial activities of the identified terpenoids were evaluated.

RESUMEN

We describe the in vitro activity of two natural isomeric ent-beyerene diterpenes, several derivatives and synthetic intermediates. Beyerenols 1 and 2 showed EC50 of 4.6 ±â€¯9.4 and 5.3 ±â€¯9.4 µg/mL against amastigotes of L. (V) brazilensis, with SI of 5.1 and 7.7, respectively. Beyerenol 1 was synthesized from stevioside. In vivo experiments with bereyenols showed cure in 50% of hamsters infected with L. (V) brazilensis topically applied as Cream I (beyerenol 1, 0.81%, w/w) and Cream III (beyerenol 2, 1.96%, w/w). These results suggest that beyerenols are potential candidates for cutaneous leishmaniasis chemotherapy by topical application. In vitro assays of amastigotes of L. (V) brazilensis showed EC50 of 1.1 ±â€¯0.1 and 1.3 ±â€¯0.04 µg/mL, with SI of 3.1 and 3.5 for hydrazone intermediates 10 and 11, respectively.

Asunto(s)

Diterpenos/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Tripanocidas/uso terapéutico , Animales , Línea Celular , Diterpenos/síntesis química , Diterpenos/farmacología , Diterpenos/toxicidad , Femenino , Humanos , Leishmania braziliensis/efectos de los fármacos , Macrófagos/efectos de los fármacos , Masculino , Mesocricetus , Tripanocidas/síntesis química , Tripanocidas/farmacología , Tripanocidas/toxicidad

RESUMEN

The oleoresin of Copaifera trees has been widely used as a traditional medicine in Neotropical regions for thousands of years and remains a popular treatment for a variety of ailments. The copaiba resins are generally composed of a volatile oil made up largely of sesquiterpene hydrocarbons, such as ß-caryophyllene, α-copaene, ß-elemene, α-humulene, and germacrene D. In addition, the oleoresin is also made up of several biologically active diterpene acids, including copalic acid, kaurenoic acid, alepterolic acid, and polyalthic acid. This review presents a summary of the ecology and distribution of Copaifera species, the traditional uses, the biological activities, and the phytochemistry of copaiba oleoresins. In addition, several biomolecular targets relevant to the bioactivities have been implicated by molecular docking methods.

Asunto(s)

Antiinflamatorios/química , Inhibidores Enzimáticos/química , Fabaceae/química , Aceites Volátiles/química , Extractos Vegetales/química , Antiinflamatorios/farmacología , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular , Aceites Volátiles/farmacología , Extractos Vegetales/farmacología