Nucleus-Independent Chemical Shift (NICS) as a Criterion for the Design of New Antifungal Benzofuranones.

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.

Analysis of Volatile Molecules Present in the Secretome of the Fungal Pathogen Candida glabrata.

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.

Anti-inflammatory and antitumor activities of the chloroform extract and anti-inflammatory effect of the three diterpenes isolated from Salvia ballotiflora Benth.

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.

Quantification of pyrazinamide, isoniazid, acetyl-isoniazid, and rifampicin by a high-performance liquid chromatography method in human plasma from patients with tuberculosis.

The aim of this study was to establish and validate an alternative high-performance liquid chromatography method for simultaneous quantification of pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin in plasma of patients under treatment for tuberculosis. The performed method was lineal (r2  > 0.99) in the range of 2.00-50.00 µg/mL for pyrazinamide, 0.50-20.00 µg/mL for both acetyl-isoniazid and isoniazid, and 1.20-25.00 µg/mL for rifampicin. Precision and trueness were demonstrated with coefficient of variation < 15% and deviations < 15%, respectively, for quality controls samples. The lower limits of quantification were 2.00, 0.50, 0.50, and 1.20 µg/mL for pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin, respectively. The method was applied for the analysis of plasma from patients with tuberculosis. This method allowed ensuring reliable quantification of the target compounds and their pharmacokinetics parameters. In general, the mean values of maximum concentration of each antituberculosis drug were located within their respective reference therapeutic ranges. However, patients with sub-therapeutic plasma concentrations of isoniazid and rifampicin were detected. This is the first analytical technique that simultaneously quantifies isoniazid, acetyl-isoniazid, rifampicin, and pyrazinamide concentrations from plasma samples by high-performance liquid chromatography with ultraviolet/visible. The proposed method could be applied for therapeutic drug monitoring and pharmacokinetics studies of the four compounds throughout the treatment of tuberculosis patients.

Anti-inflammatory and antinociceptive effects of tilifodiolide, isolated from Salvia tiliifolia Vahl (Lamiaceae).

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.

Chemical characterization, pharmacological effects, and toxicity of an ethanol extract of Celtis pallida Torr. (Cannabaceae) aerial parts.

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 µg/ml) for 5 h in peripheral blood mononuclear cells, and the acute toxicity test (500-5000 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 (10-200 mg/kg p.o.) was calculated using the castor oil test. The antinociceptive effects of CPE (50-200 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 (50-200 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 µg/ml or higher induced genotoxicity in vitro and showed low in vivo toxicity (LD50 > 5000 mg/kg p.o.). Additionally, CPE lacked (MIC > 400 µg/ml) antimicrobial activity but exerts antinociceptive (ED50 = 12.5 ±â€¯1.5 mg/kg) and antidiarrheal effects (ED50 = 2.8 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.

Antinociceptive Activity of Ent-Dihydrotucumanoic Acid Isolated from Gymnosperma glutinosum Spreng Less.

Preclinical Research The diterpene ent-dihydrotumanoic acid (DTA) was among the compounds isolated from Gymnosperma glutinosum (Spreng) Less (Asteraceae). There are no reports regarding the pharmacological effects of DTA. Cytotoxicity against cancer cells (1-250 µM), and the antibacterial (50-1400 µM) activity of DTA were evaluated using the MTT assay, and the minimum inhibitory concentration test, respectively. The antidiarrheal (1-100 mg/kg p.o.) and anti-inflammatory (2 mg/ear) effects of DTA were evaluated using castor oil and 12-O-tetradecanoylphorbol-13-acetate, respectively. The antinociceptive and sedative effects of DTA (1-100 mg/kg p.o.) were evaluated using two models of chemically-induced nociception, and the pentobarbital-induced sleeping time test, respectively. The antinociceptive mechanism of DTA was evaluated using the acetic acid writhing test with inhibitors related to pain processing pathways. The effects of DTA (10-100 mg/kg p.o.) on locomotor activity were evaluated using the rotarod test. DTA lacked cytotoxic activity (IC50 > 100 µM) on cancer cells, possessed moderate antibacterial effects against B. subtillis (MIC= 175 µM), moderate antidiarrheal and anti-inflammatory effects, and minimal vasorelaxant effects. In the formalin test, DTA showed antinociceptive effects in both phases. In the acetic acid test, DTA showed antinociceptive activity (ED50 = 50.2 ± 5.6 mg/kg) with potency similar to that of naproxen (NPX; ED50 =33.7 ± 4.5 mg/kg) an effect blocked by naloxone implicating an opioid mechanism. DTA also exerted antidiarrheal activity and showed no sedative effects or changes in locomotor activity in mice. Drug Dev Res 78 : 340-348, 2017. © 2017 Wiley Periodicals, Inc.

Theoretical Reactivity Study of Indol-4-Ones and Their Correlation with Antifungal Activity.

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 [...].

Anti-inflammatory activity of standardized dichloromethane extract of Salvia connivens on macrophages stimulated by LPS.

CONTEXT: A previous study demonstrated that the chloroform extract of Salvia connivens Epling (Lamiaceae) has anti-inflammatory activity. OBJECTIVE: Identification of the active components in the dicholorometane extract (DESC), and, standardization of the extract based in ursolic acid. MATERIAL AND METHODS: DESC was prepared by percolation with dichlromethane and after washed with hot hexane, its composition was determined by CG-MS and NMR, and standardized by HPLC. The anti-inflammatory activity was tested on acute TPA-induced mouse ear oedema at doses of 2.0 mg/ear. The cell viability of macrophages was evaluated by MTT method, and pro- and anti-inflammatory interleukin levels were measured using an ELISA kit. RESULTS: Ursolic acid, oleanolic acid, dihydroursolic acid and eupatorin were identified in DESC, which was standardized based on the ursolic acid concentration (126 mg/g). The anti-inflammatory activities of DESC, the acid mixture, and eupatorin (2 mg/ear) were 60.55, 57.20 and 56.40% inhibition, respectively, on TPA-induced ear oedema. The IC50 of DESC on macrophages was 149.4 µg/mL. DESC (25 µg/mL) significantly reduced TNF-α (2.0-fold), IL-1ß (2.2-fold) and IL-6 (2.0-fold) in macrophages stimulated with LPS and increased the production of IL-10 (1.9-fold). DISCUSSION: Inflammation is a basic response to injuries, and macrophages are involved in triggering inflammation. Macrophage cells exhibit a response to LPS, inducing inflammatory mediators, and DESC inhibits the biosynthesis of the pro-inflammatory and promote anti-inflammatory cytokines. CONCLUSION: DESC has an anti-inflammatory effect; reduced the levels of IL-1ß, Il-6 and TNF-α; and increases IL-10 in macrophages stimulated with LPS. Ursolic acid is a good phytochemical marker.

Pharmacological evaluation of 2-angeloyl ent-dihydrotucumanoic acid.

CONTEXT: Gymnosperma glutinosum (Spreng.) Less. (Asteraceae) is a bush used for the empirical treatment of pain, fever, and cancer. An ent-neo-clerodane diterpene (2-angeloyl ent-dihydrotumanoic acid; ADTA) was isolated from G. glutinosum. OBJECTIVE: This study evaluates the cytotoxic, anti-inflammatory, and antinociceptive effects of ADTA. MATERIALS AND METHODS: The cytotoxic effects of ADTA (1-350 µM) were evaluated using the MTT assay with human tumorigenic (SW-620, MDA-MB231, SKLU1, SiHa, and PC-3), and non-tumorigenic (HaCaT) cells for 48 h. The in vitro anti-inflammatory effects of ADTA (0.23-460 µM) were assessed using murine peritoneal macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The antinociceptive effects of ADTA (25-100 mg/kg p.o.) were evaluated using two in vivo models of chemical-induced nociception during 1 h. RESULTS: ADTA lacked cytotoxic activity (IC50> 100 µM) on tumorigenic cells. In non-tumorigenic cells (HaCaT), ADTA exerted low cytotoxic effects (IC50 = 273 µM). ADTA, at concentrations of 115 µM or higher, decreased the release of pro-inflammatory mediators. The maximum antinociceptive effects of ADTA in the acetic acid-induced abdominal constrictions by ADTA was found at 100 mg/kg (63%), whereas in the formalin test at phase 1 and phase 2, ADTA (100 mg/kg) decreased the licking time by 47 and 71%, respectively. CONCLUSION: The results indicate that ADTA, obtained from G. glutinosum, exerts moderate in vitro anti-inflammatory and in vivo antinociceptive effects, but lacks cytotoxic effects on human cancer cells.

Pharmacological effects and toxicity of Costus pulverulentus C. Presl (Costaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Costus pulverulentus C. Presl (Costaceae), a species endemic to Mexico, is used for the empirical treatment of cancer, pain, and inflammation. AIM OF THE STUDY: The objective of this study was to evaluate the toxicity, as well as the cytotoxic, antinociceptive, anti-inflammatory and sedative effects of an ethanol extract from Costus pulverulentus stem (CPE). MATERIALS AND METHODS: The chemical characterization of CPE was performed by Gas chromatography-mass spectrometry (GC-MS). The toxicity of CPE was evaluated using the comet assay (10-1000 µg/ml during 5h) and the acute toxicity test (500-5000 mg/kg p.o. and i.p. during 14 days). The cytotoxic effect of CPE (1-250 µg/ml) on human cancer cells was evaluated using the MTT assay. The antinociceptive effects of CPE (50-200mg/kg p.o.) were evaluated using thermal-induced nociception tests (hot plate and tail flick) and the chemical-induced nociceptive tests (acetic acid and formalin). The sedative activity of CPE (50-200mg/kg p.o.) was evaluated using the ketamine-induced sleeping time test. RESULTS: CPE showed the presence of compounds such as campesterol, stigmasterol ß-sitosterol, vanillic acid, among others. In the comet assay, CPE at 200 µg/ml or higher concentrations induced DNA damage. In the acute toxicity test, the LD50 estimated for CPE was>5000 mg/kg p.o. or i.p. CEP showed moderate cytotoxic effects on prostate carcinoma cells PC-3 cells (IC50=179 ± 23.2 µg/ml). In the chemical-induced nociception models, CPE (100 and 200mg/kg p.o.) showed antinociceptive effects with similar activity to 100mg/kg naproxen. In the thermal-induced nociception tests, CPE tested at 200mg/kg showed moderate antinociceptive effects by 28% (hot plate test) and by 25% (tail flick test). In the ketamine-induced sleeping time test, CPE showed no sedative effects. CONCLUSIONS: C. pulverulents exerts moderate cytotoxic effects in human cancer cells, moderate anti-inflammatory and antinociceptive effects. C. pulverulentus induces antinociceptive effects without inducing sedation.

Composition of the Essential Oil of Salvia ballotiflora (Lamiaceae) and Its Insecticidal Activity.

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.

Toxicity and antinociceptive effects of Hamelia patens

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.

De novo design of non-coordinating indolones as potential inhibitors for lanosterol 14-α-demethylase (CYP51).

The development of antifungal drugs that inhibit lanosterol 14-α-demethylase (CYP51) via non-covalent ligand interactions is a strategy that is gaining importance. A series of novel tetraindol-4-one derivatives with 1- and 2-(2,4-substituted phenyl) side chains were designed and synthesized based on the structure of CYP51 and fluconazole. The antifungal activities of these derivatives against eight human pathogenic filamentous fungi and yeast strains were evaluated in vitro by measuring the minimal inhibitory concentrations. Nearly all tested compounds 8a-g displayed activity against Candida tropicalis, Candida guilliermondii and Candida parapsilosis with a minimum inhibitory concentration (MIC) value until 8 µg mL(-1), on the other hand compounds 7a-g showed activity against Aspergillus fumigatus with a MIC value of 31.25 µg mL(-1). A molecular modeling study of the binding interactions between compounds 6, 7d, 8g and the active site of MtCYP51 was conducted based on the computational docking results.

Study of enzymatic hydrolysis of fructans from Agave salmiana characterization and kinetic assessment.

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.

Bioactivity of Carica papaya (Caricaceae) against Spodoptera frugiperda (Lepidoptera: Noctuidae).

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.

Fungicidal properties of the essential oil of Hesperozygis marifolia on Aspergillus flavus link.

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.

Design and synthesis of anti-MRSA benzimidazolylbenzene-sulfonamides. QSAR studies for prediction of antibacterial activity.

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.

Cecropia obtusifolia Bertol and its active compound, chlorogenic acid, stimulate 2-NBDglucose uptake in both insulin-sensitive and insulin-resistant 3T3 adipocytes.

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.