RESUMEN
The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL-1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL-1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
Asunto(s)
Antifúngicos/farmacología , Benzofuranos/farmacología , Hongos/efectos de los fármacos , Antifúngicos/química , Aspergillus niger/efectos de los fármacos , Aspergillus niger/patogenicidad , Benzofuranos/química , Candida/efectos de los fármacos , Candida/patogenicidad , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Pichia/efectos de los fármacos , Pichia/patogenicidad , Hidrocarburos Policíclicos Aromáticos/química , Hidrocarburos Policíclicos Aromáticos/farmacologíaRESUMEN
Candida albicans, Candida glabrata, Candida parapsilosis and Candida tropicalis are the four most common human fungal pathogens isolated that can cause superficial and invasive infections. It has been shown that specific metabolites present in the secretomes of these fungal pathogens are important for their virulence. C. glabrata is the second most common isolate world-wide and has an innate resistance to azoles, xenobiotics and oxidative stress that allows this fungal pathogen to evade the immune response and persist within the host. Here, we analyzed and compared the C. glabrata secretome with those of C. albicans, C. parapsilosis, C. tropicalis and the non-pathogenic yeast Saccharomyces cerevisiae. In C. glabrata, we identified a different number of metabolites depending on the growth media: 12 in synthetic complete media (SC), 27 in SC-glutamic acid and 23 in rich media (YPD). C. glabrata specific metabolites are 1-dodecene (0.09 ± 0.11%), 2,5-dimethylundecane (1.01 ± 0.19%), 3,7-dimethyldecane (0.14 ± 0.15%), and octadecane (0.4 ± 0.53%). The metabolites that are shared with C. albicans, C. glabrata, C. parapsilosis, C. tropicalis and S. cerevisiae are phenylethanol, which is synthesized from phenylalanine, and eicosane and nonanoic acid (identified as trimethylsilyl ester), which are synthesized from fatty acid metabolism. Phenylethanol is the most abundant metabolite in all fungi tested: 26.36 ± 17.42% (C. glabrata), 46.77 ± 15.58% (C. albicans), 49.76 ± 18.43% (C. tropicalis), 5.72 ± 0.66% (C. parapsilosis.) and 44.58 ± 27.91% (S. cerevisiae). The analysis of C. glabrata's secretome will allow us to further our understanding of the possible role these metabolites could play in its virulence.
Asunto(s)
Candida glabrata/metabolismo , Ácidos Grasos Volátiles/metabolismo , Especificidad de la EspecieRESUMEN
BACKGROUND: Drugs used for the treatment of diseases associated with chronic inflammation, such as cancer and rheumatoid arthritis have the potential to cause undesirable side-effects, which might result in patients ending treatment prematurely. However, plants are a viable option for the treatment of inflammatory diseases. In this study, we assessed the in vivo and in vitro anti-inflammatory activity, and the antitumor effects of the chloroform extract of Salvia ballotiflora (ECL). The pro-apoptotic effects of ECL in CT26 cells were also determined. METHODS: The chloroform extract of Salvia ballotiflora (ECL) was standardized using 19-deoxyicetexone (DEOX) as a phytochemical marker. The anti-inflammatory activity of ECL was determined on acute and chronic inflammatory models using the TPA-induced mouse ear edema assay. The antitumor activity of ECL was evaluated by the subcutaneous inoculation of CT26 cells on the back of Balb/c mice. In vitro CT26 cell death induced by ECL was determined by Annexin V/propidium iodide staining assay using flow cytometry. ECL and the diterpenes isolated from the chloroform extract included 19-deoxyicetexone (DEOX), icetexone (ICT), and 7,20-dihydroanastomosine (DAM), which were tested in LPS-stimulated J774A.1 macrophages to quantify pro-inflammatory cytokine levels. The in vitro anti-arthritic activity of ECL was determined using the bovine serum protein (BSP) denaturation assay. RESULTS: ECL exerted anti-inflammatory activities in acute (84% of inhibition, 2 mg/ear) and chronic models (62.71%, at 100 mg/kg). ECL showed antitumor activity at 200 mg/kg and 300 mg/kg, reducing tumor volume by 30 and 40%, respectively. ECL (9.5 µg/mL) induced in vitro apoptosis in CT26 cells by 29.1% (48 h of treatment) and 93.9% (72 h of treatment). ECL (10 µg/ml) decreased levels of NO (53.7%), pro-inflammatory cytokines IL-6 (44.9%), IL-1ß (71.9%), and TNF-α (40.1%), but increased the production of the anti-inflammatory cytokine IL-10 (44%). The diterpenes DEOX, ICT, and DAM decreased levels of NO (38.34, 47.63, 67.15%), IL-6 (57.84, 60.45, 44.26%), and TNF-α (38.90, 31.30, 32.83%), respectively. ECL showed in vitro antiarthritic activity (IC50 = 482.65 µg/mL). CONCLUSIONS: ECL exhibited anti-inflammatory and anti-tumor activities. Furthermore, the diterpenes DEOX, DAM, and ICT showed anti-inflammatory activity by reducing levels of NO, TNF-α, and IL-6.
Asunto(s)
Antiinflamatorios no Esteroideos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos/farmacología , Extractos Vegetales/farmacología , Salvia/química , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/toxicidad , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/toxicidad , Apoptosis/efectos de los fármacos , Artritis/tratamiento farmacológico , Línea Celular Tumoral , Cloroformo , Citocinas/inmunología , Diterpenos/aislamiento & purificación , Diterpenos/toxicidad , Edema/tratamiento farmacológico , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Óxido Nítrico/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Salvia tiliifolia Vahl (Lamiaceae) is used for the empirical treatment of pain and inflammation. The diterpenoid tilifodiolide (TFD) was isolated from Salvia tiliifolia. The in vitro anti-inflammatory effects of TFD (0.1-200 µM) were assessed using murine macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The in vivo anti-inflammatory activity of TFD was assessed using the carrageenan-induced paw edema test for 6 h. The antinociceptive effects of TFD were evaluated using the formalin test and the acetic acid induced-writhing test. The effects of TFD on locomotor activity were assessed using the open field test and the rotarod test. TFD inhibited the production of TNF-α (IC50 = 5.66 µM) and IL-6 (IC50 = 1.21 µM) in macrophages. TFD (200 mg/kg) showed anti-inflammatory effects with similar activity compared to 10 mg/kg indomethacin. The administration of TFD induced antinociception in the phase 1 (ED50 = 48.2 mg/kg) and the phase 2 (ED50 = 28.9 mg/kg) of the formalin test. In the acetic acid assay, TFD showed antinociceptive effects (ED50 = 32.3 mg/kg) with similar potency compared to naproxen (ED50 = 36.2 mg/kg). In the presence of different inhibitors in the acetic acid assay, only the co-administration of TFD and naloxone reverted the antinociceptive activity shown by TFD alone. TFD did not affect locomotor activity in mice. TFD exerts in vitro and in vivo anti-inflammatory activity and in vivo antinociceptive effects.
Asunto(s)
Analgésicos/farmacología , Antiinflamatorios/farmacología , Diterpenos/farmacología , Dimensión del Dolor/efectos de los fármacos , Salvia/química , Animales , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Indometacina/farmacología , Interleucina-6/metabolismo , Macrófagos/metabolismo , Masculino , Ratones , Actividad Motora , Naloxona/farmacología , Naproxeno/farmacología , Prueba de Desempeño de Rotación con Aceleración Constante , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Celtis pallida Torr (Cannabaceae) is employed as a folk medicine for the treatment of inflammation, pain, skin infections, and diarrhea, among other diseases. AIM OF THE STUDY: The purpose of this work was to assess the chemical composition, the in vitro and in vivo toxicity, the antimicrobial, anti-inflammatory, antidiarrheal, antinociceptive, locomotor, and sedative effects of an ethanolic extract obtained from Celtis pallida aerial parts (CPE). MATERIALS AND METHODS: The composition of CPE was carried out by GC-MS. The in vitro and in vivo toxic activity of CPE was estimated with the comet assay (10-1000⯵g/ml) for 5â¯h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000â¯mg/kg p.o.), for 14 days, respectively. The antimicrobial effect of CPE was evaluated using the minimum inhibitory concentration (MIC) assay, whereas the antidiarrheal activity (10-200â¯mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200â¯mg/kg p.o.) were estimated with the acetic acid and formalin tests, as well as the hot plate test. The sedative and locomotor activities of CPE (50-200â¯mg/kg p.o.) were assessed with the pentobarbital-induced sleeping time test and the rotarod test, respectively. RESULTS: The main compound found in CPE was the triterpene ursolic acid (22% of the extract). CPE at concentrations of 100⯵g/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000â¯mg/kg p.o.). Additionally, CPE lacked (MIC > 400⯵g/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5⯱â¯1.5â¯mg/kg) and antidiarrheal effects (ED50 = 2.8â¯mg/kg), without inducing sedative effects or altering the locomotor activity. The antinociceptive activity of CPE suggests the participation of adrenoceptors, as well as the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway. CONCLUSION: C. pallida exerts its antinociceptive effects probably mediated by the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway.
Asunto(s)
Analgésicos/farmacología , Cannabaceae , Dimensión del Dolor/efectos de los fármacos , Componentes Aéreos de las Plantas , Extractos Vegetales/farmacología , Analgésicos/aislamiento & purificación , Analgésicos/toxicidad , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/toxicidad , Antidiarreicos/aislamiento & purificación , Antidiarreicos/farmacología , Antidiarreicos/toxicidad , Relación Dosis-Respuesta a Droga , Etanol/farmacología , Ratones , Ratones Endogámicos BALB C , Pruebas de Mutagenicidad/métodos , Dimensión del Dolor/métodos , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , UlmaceaeRESUMEN
Chemical reactivity descriptors of indol-4-ones obtained via density functional theory (DFT) and hard-soft acid-base (HSAB) principle were calculated to prove their contribution in antifungal activity [...].
Asunto(s)
Antifúngicos/química , Antifúngicos/farmacología , Indoles/química , Indoles/farmacología , Modelos Químicos , Modelos Moleculares , Algoritmos , Hongos/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Electricidad Estática , Relación Estructura-ActividadRESUMEN
Essential oils can be used as an alternative to using synthetic insecticides for pest management. Therefore, the insectistatic and insecticidal activities of the essential oil of aerial parts of Salvia ballotiflora (Lamiaceae) were tested against the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae). The results demonstrated insecticidal and insectistatical activities against this insect pest with concentrations at 80 µg·mL(-1) resulting in 20% larval viability and 10% pupal viability. The larval viability fifty (LV50) corresponded to a concentration of 128.8 µg·mL(-1). This oil also increased the duration of the larval phase by 5.5 days and reduced the pupal weight by 29.2% withrespect to the control. The GC-MS analysis of the essential oil of S. ballotiflora showed its main components to be caryophyllene oxide (15.97%), and ß-caryophyllene (12.74%), which showed insecticidal and insectistatical activities against S. frugiperda. The insecticidal activity of ß-caryophyllene began at 80 µg·mL(-1), giving a larval viability of 25% and viability pupal of 20%. The insectistatic activity also started at 80 µg·mL(-1) reducing the pupal weight by 22.1% with respect to control. Caryophyllene oxide showed insecticidal activity at 80 µg·mL(-1) giving a larval viability of 35% and viability pupal of 20%.The insectistatic activity started at 400 µg·mL(-1) and increased the larval phase by 8.8% days with respect to control. The LV50 values for these compounds were 153.1 and 146.5 µg·mL(-1), respectively.
Asunto(s)
Insecticidas/química , Insecticidas/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Salvia/efectos de los fármacos , Animales , Larva/efectos de los fármacos , Componentes Aéreos de las Plantas/química , Sesquiterpenos Policíclicos , Sesquiterpenos/química , Sesquiterpenos/farmacología , Spodoptera/efectos de los fármacosRESUMEN
Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae), a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg) was evaluated in acute (14 days) and subacute (28 days) assays. In the subacute assay, a blood analysis (both hematology and chemistry) was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg) were evaluated using thermal-induced nociception (hot plate) and the chemical-induced nociceptive tests (acid acetic and formalin). In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o.) showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17%) and 200 mg/kg (25%) showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.
RESUMEN
Fructans were extracted from Agave salmiana juice, characterized and subjected to hydrolysis process using a commercial inulinase preparation acting freely. To compare the performance of the enzymatic preparation, a batch of experiments were also conducted with chicory inulin (reference). Hydrolysis was performed for 6 h at two temperatures (50, 60 °C) and two substrate concentrations (40, 60 mg/ml). Hydrolysis process was monitored by measuring the sugars released and residual substrate by HPLC. A mathematical model which describes the kinetics of substrate degradation as well as fructose production was proposed to analyze the hydrolysis assessment. It was found that kinetics were significantly influenced by temperature, substrate concentration, and type of substrate (P < 0.01). The extent of substrate hydrolysis varied from 82 to 99%. Hydrolysis product was mainly constituted of fructose, obtaining from 77 to 96.4% of total reducing sugars.
Asunto(s)
Agave/enzimología , Fructanos/química , Insulisina/química , Activación Enzimática , Hidrólisis , Cinética , Especificidad por SustratoRESUMEN
The composition of a chloroform seed extract of C. papaya was determined by GC-MS. Nineteen compounds were identified, with oleic (45.97%), palmitic (24.1%) and stearic (8.52%) acids being the main components. The insecticidal and insectistatic activities of the extract and the three main constituents were tested. Larval duration increased by 3.4 d and 2.5 d when the extract was used at 16,000 and 9,600 ppm, respectively, whereas the pupal period increased by 2.2 d and 1.1 d at the same concentrations. Larval viability values were 0%, 29.2%, and 50% when the extract was applied at 24,000, 16,000, and 9,600 ppm, respectively; pupal viability was 42.9% and 66.7% at 16,000 and 9,600 ppm; and pupal weight decreased by 25.4% and 11.5% at 16,000 and 9,600 ppm. The larval viability of the main compounds was 33.3%, 48.5%, and 62.5% when exposed to 1,600 ppm of palmitic acid, oleic acid, or stearic acid, respectively.
Asunto(s)
Carica/química , Insecticidas/farmacología , Extractos Vegetales/farmacología , Semillas/química , Spodoptera/efectos de los fármacos , Animales , Cloroformo/química , Ácidos Grasos/química , Femenino , Cromatografía de Gases y Espectrometría de Masas , Insecticidas/química , Insecticidas/aislamiento & purificación , Insecticidas/toxicidad , Larva/efectos de los fármacos , Larva/crecimiento & desarrollo , Dosificación Letal Mediana , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/toxicidad , Spodoptera/crecimiento & desarrolloRESUMEN
The chemical composition of the essential oil from Hesperozygis marifolia was analyzed by gas chromatography-mass spectrometry (GC-MS), and fourteen compounds were identified. (R)-pulegone (40.75%), isomenthone (30.34%) and menthone (4.46%) were found to be the main components of the oil. The essential oil at a concentration of 2.0 mg/mL and (R)-pulegone at concentration of 0.8 mg/mL completely inhibited the growth of Aspergillus flavus Link. The fungicidal effects of this essential oil warrant further research into its potential for commercial use.
Asunto(s)
Aspergillus flavus/efectos de los fármacos , Fungicidas Industriales/farmacología , Lamiaceae/química , Aceites Volátiles/farmacología , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de Masas , Pruebas de Sensibilidad MicrobianaRESUMEN
A series of benzimidazolylbenzenesulfonamide compounds containing electron-releasing and electron-withdrawing substituents were synthesized and tested for their in vitro antibacterial activity. Two BZS compounds showed strong antibacterial activity against methicillin-resistant Staphylococcus aureus and Bacillus subtilis. Quantitative studies of their structure-activity relationship using a simple linear regression analysis were applied to explore the correlation between the biological activity and the charges on acidic hydrogen atoms in the synthesized compounds.
Asunto(s)
Antibacterianos/síntesis química , Antibacterianos/farmacología , Sulfonamidas/síntesis química , Sulfonamidas/farmacología , Antibacterianos/química , Diseño de Fármacos , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad Cuantitativa , Análisis Espectral/métodos , Sulfonamidas/químicaRESUMEN
ETHNOPHARMACOLOGICAL IMPORTANCE: Cecropia obtusifolia Bertol (Cecropiaceae) is a plant extensively used for the empirical treatment of type 2 diabetes in México. Although some of its hypoglycemic principles have been described, their mechanisms of action remain unclear. AIM OF THE STUDY: To investigate the anti-diabetic mechanisms of Cecropia obtusifolia aqueous extract (CAE) and its active compound chlorogenic acid (CGA). MATERIALS AND METHODS: Non-toxic concentrations of CAE and CGA were assayed on the adipogenesis and 2-NBDglucose uptake in 3T3-F442A murine adipocytes. RESULTS: Added to adipogenic medium, CAE 70 microg/ml induced a modest increment (20%) in 3T3 adipogenesis whereas CGA did not affect adipogenesis at any of the tested concentrations (0.1-100 microM). Both preparations stimulated 2-NBDG uptake in adipocytes by 51% (CAE) and 176% (CGA) in the absence of insulin, and by 174% (CAE) and 404% (CGA) in the presence of the hormone. CAE and CGA also stimulated the 2-NBDG uptake in insulin-resistant 3T3 adipocytes by 35% and 141%, respectively, compared with the incorporation shown by insulin-sensitive adipocytes stimulated by the hormone. The potency of CGA to stimulate 2-NBDG uptake was comparable to the anti-diabetic drug rosiglitazone. CONCLUSION: Cecropia obtusifolia and CGA exert their anti-diabetic effects stimulating glucose uptake in both insulin-sensitive and insulin-resistant adipocytes without appreciable pro-adipogenic effects.