New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design,synthesis and biological evaluation as potential anti-inflammatory and analgesic agents

A new series of 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives 10a-h was designed and synthesized for evaluation as selective COX-2 inhibitors, anti-inflammatory agents and as analgesic agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compounds 10a, 10b, 10e and 10f were the most COX-2 selective compounds (S.I. = 10.76, 10.87, 8.69 and 9.14 respectively), the most potent anti-inflammatory derivatives (ED₅₀ = 65.7, 60.2, 76.3 and 107.4 μmol/kg respectively) in comparison with Celecoxib (COX-2 S.I. = 8.61, ED₅₀ = 82.2 μmol/kg) and were less ulcerogenic (ulcer indexes = 1.22–3.02) than Ibuprofen (ulcer index = 20.25) and comparable to Celecoxib (ulcer index = 2.93). The four derivatives (10a, 10b, 10e and 10f) showed considerable analgesic activities which are clearly parallel to their anti-inflammatory activities.     

Discovery of novel analgesic and anti-inflammatory 3-arylamine-imidazo[1,2-a]pyridine symbiotic prototypes

We describe herein the design, synthesis and pharmacological evaluation of novel 3-arylamine-imidazo[1,2-a]pyridine derivatives structurally designed as novel symbiotic prototypes presenting analgesic and anti-inflammatory properties. The derivatives obtained were submitted to in vivo assays of nociception, hyperalgesia and inflammation, and to in vitro assays of human PGHS-2 inhibition. These assays allowed the identification of compound LASSBio-1135 (3a) as an anti-inflammatory and analgesic symbiotic prototype. This compound inhibited moderately the human PGHS-2 enzyme activity (IC₅₀ = 18.5 μM) and reverted the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) similarly to p38 MAPK inhibitor SB-203580 (2). Additionally, LASSBio-1135 (3a) presented activity similar to celecoxib (1) regarding the reduction of the carrageenan-induced rat paw edema (33% of inhibition at 100 μmol/kg, po). We also discovered derivatives LASSBio-1140 (3c) and LASSBio-1141 (3e) as analgesic and anti-inflammatory prototypes, which were able to attenuate the capsaicin-induced thermal hyperalgesia (100 μmol/kg, po) and reduce the carrageenan-induced paw edema (ED₅₀ = 11.5 μmol/kg (3.3 mg/kg) and 14.5 μmol/kg (4.1 mg/kg), respectively), being both more active than celecoxib (1), despite the fact that their effects involve a different mechanism of action. Additionally, derivative LASSBio-1145 (3j) showed remarkable analgesic (ED₅₀ = 22.7 μmol/kg (8.9 mg/kg)) and anti-inflammatory (ED₅₀ = 8.7 μmol/kg (3.4 mg/kg)) profile in vivo (100 μmol/kg; po), in AcOH-induced abdominal constrictions in mice and carrageenan-induced rat paw edema models, respectively, being a novel orally-active anti-inflammatory drug candidate that acts as a selective PGHS-2 inhibitor (IC₅₀ = 2.8 μM).     

A new δ-tocotrienolic acid derivative and other constituents from the cones of Cedrus atlantica and their in vitro antimicrobial activity

The phytochemical and antimicrobial properties of the cones of Cedrus atlantica (Endl) Manetti ex Carrière were investigated. Two new compounds (1,2) and nineteen known compounds (3–21) were isolated. Their structures were established by mass spectrometry (HRESIMS), 1D, 2D NMR and by comparison with literature data. Antimicrobial activity of hydromethanolic extract against a panel of 22 bacteria and yeasts showed an interesting antimicrobial activity. All compound purified from this extract were tested against S. aureus by bioautography. MIC values of the most active compounds were determined using a serial dilution technique. The results showed strong antibacterial activity of the abietane diterpenes 10, 11, 14, 15, 16 and 17. Dehydroabietic acid (17) was the most potent against Enterococcus faecalis (MIC = 15.1 = μg/mL), a multi-resistant commensal bacterium which can cause the fatal infections in humans.     

Chemistry,antioxidant and antimicrobial potential of nutmeg (Myristica fragrans Houtt)

Antioxidant and antimicrobial activities of nutmeg (Myristica fragrans Houtt) seed extracts were evaluated. Seeds were extracted with acetone, ethanol, methanol, butanol and water. All the extracts have shown significant antioxidant and antimicrobial activities against the tested microorganisms. Among all extracts, acetone extract has shown the highest antioxidant activity. The acetone extract showed 93.12 ± 1.48 mg gallic acid equivalents (GAE)/100 g dry weight total phenolic content, DPPH scavenging activity of 63.04 ± 1.56%, chelating activity of 64.11 ± 2.21% and 74.36 ± 1.94% inhibition of β-carotene bleaching, at 1 mg/mL extract concentration. Out of all extracts, acetone extract was able to exert antimicrobial activity against all tested bacteria and fungi. Acetone extract has shown the strongest antibacterial and antifungal activity with Staphylococcus aureus (13.8 ± 0.42 mm) and Aspergillus niger (14.4 ± 0.37 mm), respectively. GC–MS analysis of acetone extract has revealed the presence of 32 compounds of extract representing 99.49%. Sabinene (28.61%) has shown the highest occurrence in the extract. β-Pinene (10.26), α-pinene (9.72), myristicin (4.30%), isoeugenol (2.72%), p-cymene (1.81%), carvacrol (1.54%), eugenol (0.89%) and β-caryophellene (0.82%) were reported as possible contributor for antioxidant and antimicrobial activity of nutmeg.     

Antibacterial activities of the methanol extracts of Albizia adianthifolia,Alchornea laxiflora,Laportea ovalifolia and three other Cameroonian plants against multi-drug resistant Gram-negative bacteria

In the last 10 years, resistance in Gram-negative bacteria has been increasing. The present study was designed to evaluate the in vitro antibacterial activities of the methanol extracts of six Cameroonian medicinal plants Albizia adianthifolia, Alchornea laxiflora, Boerhavia diffusa, Combretum hispidum, Laportea ovalifolia and Scoparia dulcis against a panel of 15 multidrug resistant Gram-negative bacterial strains. The broth microdilution was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the extracts. The preliminary phytochemical screening of the extracts was conducted according to the reference qualitative phytochemical methods. Results showed that all extracts contained compounds belonging to the classes of polyphenols and triterpenes, other classes of chemicals being selectively distributed. The best antibacterial activities were recorded with bark and root extracts of A. adianthifolia as well as with L. ovalifolia extract, with MIC values ranging from 64 to 1024 μg/mL on 93.3% of the fifteen tested bacteria. The lowest MIC value of 64 μg/mL was recorded with A. laxiflora bark extract against Enterobacter aerogenes EA289.Finally, the results of this study provide evidence of the antibacterial activity of the tested plants and suggest their possible use in the control of multidrug resistant phenotypes.     

Antimicrobial and cytotoxic activities of the crude extracts of Dietes bicolor leaves,flowers and rhizomes

The crude extracts of Dietes bicolor leaves, flowers and rhizomes were subjected to comparative antimicrobial screening against two Gram-positive, two Gram-negative bacteria and four fungal strains using the agar well diffusion method. The minimum inhibitory concentrations (MIC) of the tested extracts were also determined. Furthermore, the cytotoxic activity was evaluated. D. bicolor extracts generally demonstrated notable broad spectrum antimicrobial activities (MIC values ≤ 500 μg/mL) against all tested pathogens. D. bicolor leaf extract showed potent broad spectrum antimicrobial activity with MIC values ranging between 0.24 and 31.25 μg/mL against all tested pathogens. Moreover, the flowers extract exhibited promising antimicrobial activities, displaying MIC values ranging between 1.95 and 125 μg/mL against the tested bacteria and fungi. However, the rhizomes extract showed moderate antimicrobial activity with MIC values ranging between 31.25 and 500 μg/mL. Despite the potent antimicrobial activity of D. bicolor extracts, they were ineffective as cytotoxic agents against nine tested cancer cell lines, displaying 50% inhibitory concentration (IC₅₀) values above 100 μg/mL. The reported potent antimicrobial activity along with the lack of measurable cytotoxic activity indicated that the antimicrobial activity of D. bicolor crude extracts is mediated through a mechanism other than cytotoxicity. These results suggest that D. bicolor can act as a potential source for natural antibacterial and antifungal agents with a good safety profile at a preliminary level.     

Design,synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore

A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a–l was designed and synthesized via cyclization of chalcones 8a–f with 4-amino/methanesulfonylphenylhydrazine hydrochloride 9a–b. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity, ulcerogenic liability and analgesic activity. All compounds were more COX-2 inhibitors than COX-1. While most compounds showed good anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h) were the most potent derivatives (ED₅₀ = 55.78, 53.99, 67.65 and 69.20 μmol/kg respectively) in comparison with celecoxib (ED₅₀ = 82.15 μmol/kg). Compounds 10a, 10b, 10g and 10h (ulcer index = 2.68, 1.20, 2.63 and 2.66 respectively) showed less ulceration effect than celecoxib (ulcer index = 2.90). Also, Compounds 10a, 10b, 10g and 10h showed analgesic activity higher than celecoxib and comparable to that of ibuprofen. In addition, molecular docking studies were performed for compounds 10a, 10b, 10g and 10h and the results were in agreement with that obtained from the in vitro COX inhibition assays.     

Phytosynthesis of silver nanoparticles from Jatropha integerrima Jacq. flower extract and their possible applications as antibacterial and antioxidant agent

Jatropha integerrima Jacq. flower extract was used for the synthesis of silver nanoparticles in the current study. Various spectroscopic analyses were used to characterize the synthesized nanoparticles (JIF-AgNPs). The antibacterial efficacy of JIF-AgNPs was studied by well diffusion and microdilution techniques. In addition, the impact of JIF-AgNPs on free radicals was evaluated. On the ultraviolet–visible spectrum, the nanoparticles exhibit the highest absorbance at 422 nm. Based on the Fourier transform infrared spectrum, phenols and amino acids were involved in capping the JIF-AgNPs. Crystalline sphere-shaped nanoparticles with an average size of 50.07 nm and zeta potential of ?19.0 mV were confirmed by X-ray diffraction, transmission electron microscopy, and dynamic light scattering analysis respectively. The JIF-AgNPs exhibit the highest and lowest growth inhibitory activity towards E. coli and B. subtilis. The minimal inhibitory concentration of JIF-AgNPs against E. coli, K. pneumoniae, S. aureus, and B. subtilis were 2.5, 5.0, 5.0, and 7.5 μg/mL, respectively. The JIF-AgNPs exhibited significant radical scavenging activities against DPPH (IC₅₀-32.5 ± 0.06 µg/mL), hydroxyl (IC₅₀-25 ± 0.09 µg/mL), Superoxide (IC₅₀-42.5 ± 0.13 µg/mL), and ABTs (IC₅₀-33.5 ± 0.15 µg/mL). Thus, synthesized nanoparticles were a good alternative to develop an antibacterial and antioxidant agent.     

Biological activities of two macroalgae from Adriatic coast of Montenegro

In the present investigation the acetone extracts of macroalgae Ulva lactuca and Enteromorpha intestinalis were tested for antioxidant, antimicrobial and cytotoxic potential. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic and flavonoid compounds in extracts. As a result of the study, U. lactuca extract was found to have a better free radical scavenging activity (IC₅₀ = 623.58 μg/ml) than E. intestinalis extract (IC₅₀ = 732.12 μg/ml). Moreover, the tested extracts had effective ferric reducing power and superoxide anion radical scavenging. The total content of phenol in extracts of U. lactuca and E. intestinalis was 58.15 and 40.68 μg PE/mg, while concentrations of flavonoids were 39.58 and 21.74 μg RE/mg, respectively. Furthermore, among the tested species, extracts of U. lactuca showed a better antimicrobial activity with minimum inhibitory concentration values ranging from 0.156 to 5 mg/ml, but it was relatively weak in comparison with standard antibiotics. Bacillus mycoides and Bacillus subtilis were the most susceptible to the tested extracts. Contrary to this Aspergillus flavus, Aspergillus fumigatus and Penicillium purpurescens were the most resistant. Finally, cytotoxic activity of tested extracts was evaluated on four human cancer cell lines. Extract of E. intestinalis expressed the stronger cytotoxic activity towards all tested cell lines with IC₅₀ values ranging from 74.73 to 155.39 μg/ml.     

Proinflammatory,anti-inflammatory cytokines and adiponkines in students with central obesity

Several studies have investigated the correlation between central obesity and inflammatory cytokines and the anti-inflammatory cytokine adiponectin. But, the correlation between central obesity and the anti-inflammatory cytokines IL-4, IL-5 has not been studied yet. Thus, we aimed to study the IL-4 and IL-5 correlation to central obesity in adolescent Egyptian girls among proinflammatory and anti-inflammatory cytokines. The study was carried out on 86 obese adolescent girls (BMI > 95 percentile) divided into two groups according to central obesity. The group I with waist to hip ratio <0.8 as a control and group II with waist to hip ratio >0.8 (central obesity). There was a significant increase in TNF-alpha (p < 0.0001), and IL-1β (p < 0.0001), as proinflammatory cytokines in group II, as compared to their corresponding group I. Group II showed a significant increase in the anti-inflammatory cytokines IL-4 and IL-5 than group I at (p < 0.0001) and (p < 0.0005) respectively. In addition there was a significant decrease in the anti-inflammatory adiponectin and an increase in the inflammatory leptin levels in group II at (p < 0.0001) and (p < 0.0001) respectively in comparison to group I. A high positive correlation has been observed between waist to hip ratio, leptin, TNF-α, IL-1-β, IL-4 and IL-5 at (r = 0.331, p < 0.03), (r = 0.559, p < 0.001), (r = 0.435, p < 0.004), (r = 0.509, p < 0.001), (r = 0.550, p < 0.0015), in group II respectively and a high negative one with adiponectin at (r = ?0.410, p < 0.0001). We concluded that central obesity lowers adiponectin plasma level through increasing proinflammatory adipokines such as TNF-α, IL-1β, leptin. Further studies are needed to explore the positive correlation we found between central obesity and the anti-inflammatory cytokines IL-4 and IL-5 known to be associated with bronchial asthma.     

Safety of Prunus africana and Warburgia ugandensis in asthma treatment

The aim of the study was to determine the possible cytotoxicity of the aqueous stem bark extracts of Prunus africana and Warburgia ugandensis to Vero E6 cells and acute toxicity in BALB/c mice. Despite being some of the most popular medicinal plants used in Africa, little is known about the safety. In-vitro cytotoxicity tests on Vero E6 cells were investigated using MTT assay to assess the safety of the two plant extracts. Vero E6 cells on growing to confluence were incubated with different drug concentrations for 48 h for the drug to take effect. Viability of the cells was measured by a scanning multiwell spectrophotometer, color intensity being equivalent to viable cells which reduce MTT to soluble formazan crystals. This was done by determining the CC₅₀ of the extracts, CC₅₀ being the concentration of the dose of the compound/extract that kills 50% of the cells. In acute toxicity a total of 55 mice were used. Mice were divided into eleven groups of 5 mice, one group served as negative control and ten groups received oral gavage doses at 500, 889.56, 1581.6, 2812.15 or 5000 mg/kg body weight once. Mortality and other signs of toxicity were recorded within 24 h and the weights of the surviving mice taken for 14 days thereafter. P. africana had CC₅₀ of 104.08 μg/ml while W. ugandensis had CC₅₀ > 250 μg/ml and both were classified as not cytotoxic. There was no mortality observed in groups of mice that received P. africana extracts at 500 and 889.56 mg/kg body weight. There was 20%, 60% and 100% mortality observed within 24 h for mice that received P. africana extracts at 1581.64, 2812.15 and 5000 mg/kg body weight respectively. Lethal dose (LD₅₀) for P. africana was 2201.207 mg/kg body weight. W. ugandensis extracts had no mortality recorded in all dose levels and the LD₅₀ was > 5000 mg/kg body weight. The weights of mice that survived the entire 14 days in all groups increased and were not significantly different from that of controls p > 0.05. From the in vitro and in vivo studies, the two extracts were safe to use. Though with their customary value among many Kenyan communities in management of asthma among other ailments there is a need for further validation of any anti-asthmatic properties and responsible chemical compounds to augment the findings.     

Isolation and identification of antibacterial compounds from Thymus kotschyanus aerial parts and Dianthus caryophyllus flower buds

Aim of the studyThe aerial parts of Thymus kotschyanus Boiss. and Hohen. (Lamiaceae) and flower buds of Dianthus caryophyllus L. (Caryophyllaceae) have been traditionally implemented in the treatment of wounds, throat and gum infections and gastro-intestinal disorder by the indigenous people of northern Iraq, although the compounds responsible for the medicinal properties have not been identified. In this study, antibacterial compounds from both plants were isolated and characterized, and the biological activity of each compound was assessed individually and combined.Materials and methodsCompounds were isolated and characterized from the extracted essential oils of both plants using different spectral techniques: TLC, FTIR spectra and HPLC. The minimum inhibitory concentrations MIC values for the compounds were assessed individually and combined based on a microdilution and the checkerboard method in 96 multi-well microtiter plates.ResultsTwo known compounds were isolated from the essential oils of both plants and were identified as thymol and eugenol. The isolated compounds were investigated for their single and combined antibacterial activities against seven selected pathogenic bacteria; Staphylococcus aureus, Bacillus cereus, Listeria monocytogenes, Proteus mirabilis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Thymol MIC values ranged from 15.6 to 250.0 μg/ml and B. cereus was found to be the most sensitive pathogen with a MIC value of 15.6 μg/ml. Eugenol achieved stronger MIC values against most tested pathogens and the best MIC value (15.6 μg/ml) was observed against B. cereus, L. monocytogenes and K. pneumoniae whereas, S. aureus, P. mirabilis and E. coli were inhibited with a MIC value of 31.2 μg/ml. Combination results had antibacterial enhancement against most pathogens and the best synergistic result was seen against P. mirabilis and E. coli.ConclusionsThe isolation of two antibacterial compounds from Thymus kotschyanus aerial parts and Dianthus caryophyllus flower buds validates the use of these species in the treatment of throat and gum infections, wound-healing and gastro-intestinal disorder.     

Apolipoprotein A-I inhibits chemotaxis,adhesion, activation of THP-1 cells and improves the plasma HDL inflammatory index

The anti-inflammatory effects of high density lipoprotein (HDL) are well described, however, such effects of Apolipoprotein A-I (ApoA-I) are less studied. Building on our previous study, we further explored the mechanism of anti-inflammatory effects of ApoA-I, and focused especially on the interaction between monocyte and endothelial cells and plasma HDL inflammatory index in LPS-challenged rabbits. Our results show that ApoA-I significantly decreased LPS-induced MCP-1 release from THP-1 cells and ox-LDL-induced THP-1 migration ratio (P < 0.01, respectively). ApoA-I significantly decreased sL-selectin, sICAM-1 and sVCAM-1 release (P < 0.01, P < 0.01, P < 0.05, respectively) from LPS-stimulated THP-1 cells. Furthermore, ApoA-I significantly inhibited LPS-induced CD11b and VCAM-1 expression on THP-1 cells (P < 0.01, P < 0.05, respectively). ApoA-I diminished LPS-induced mCD14 expression (P < 0.01) and NFκB nuclear translocation in THP-1 cells. After single dose treatment of ApoA-I, the value of plasma HDL inflammatory index in LPS-challenged rabbits was improved significantly (P < 0.05). These results suggest that ApoA-I can inhibit chemotaxis, adhesion and activation of human monocytes and improve plasma HDL inflammatory index with presenting beneficial anti-inflammatory effects.     

Seed and forage yield,and forage quality determinants of nine legume shrubs in a non-tropical dryland environment

The objective was to identify legume shrub species for development of agroforestry technologies based on seed and forage (leaves and twigs < 10 mm diameter) yield, and determinants of forage quality. Ten individual plants of Bituminaria bituminosa ‘Ecotypes 1’, B. bituminosa ‘Ecotypes 2’, Medicago citrina, and M. arborea from Spain; Colutea istria and Onobrychis aurantiaca from Syria; C. istria from Jordan; Chamaecytisus mollis from Morocco; and Coronilla glauca from France were randomly selected from plots established in a non-tropical dryland environment in northwest Syria in 2000. Five individual plants of each species were cut back to 0.5 m above ground in March 2004. Coppice regrowths were pruned in December 2004 and April 2005 to determine forage yield and proportion of forage in the total above ground biomass (PEFB). Forage samples were analyzed for concentrations of crude protein (CP), lignin(sa), acid detergent fibre (ADFom), neutral detergent fibre (aNDFom), in vitro organic matter (OM) digestibility (IVOMD), and in vitro 24 h gas production (IVGP24h). Matured seeds were hand harvested from the remaining five plants of each species to estimate seed yield. Forage (21–250 kg DM/ha) and seed (0–200 kg DM/ha) yields; PEFB (0.22–0.96); and concentrations of CP (85–115 g/kg DM), lignin(sa) (14–42 g/kg DM), ADFom (94–170 g/kg DM), aNDFom (122–217 g/kg DM), IVOMD (456–617 g/kg OM), and IVGP24h (27–42 ml 200 mg/DM) varied (P<0.05) among shrub species. The IVOMD and IVGP24h were positively correlated (r = 0.75, P<0.032), whereas IVOMD and IVGP24h were negatively correlated with ADFom, lignin(sa) and aNDFom. In terms of forage and seed yields and determinants of forage quality, C. istria from Jordan, M. arborea, B. bituminosa ‘Ecotype-2’, C. istria and O. aurantiaca have higher potential than C. mollis, C. glauca and B. Bituminosa ‘Ecotype-1’ for the development of agroforestry technologies in non-tropical dry areas.     

Design,synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity,anti-inflammatory activity and gastric safety profile

Two series of new thiazolidin-4-one derivatives 4a–c and 8a–e were designed and prepared. All the synthesized compounds were evaluated for their in vitro COX-2 selectivity and anti-inflammatory activity in vivo. Compounds 8c and 8d showed the best overall in vitro COX-2 selectivity (selectivity indexes of 4.56 and 5.68 respectively) and in vivo activities (edema inhibition % = 61.8 and 67 after 3 h, respectively) in comparison with the reference drug celecoxib (S.I. = 7.29, edema inhibition % = 60 after 3 h). In addition, 8c and 8d were evaluated for their mean effective anti-inflammatory doses (ED₅₀ = 27.7 and 18.1 μmol/kg respectively, celecoxib ED₅₀ = 28.2 μmol/kg) and ulcerogenic liability (reduction in ulcerogenic potential versus celecoxib = 85%, 92% respectively. Molecular docking studies were performed and the results were in agreement with that obtained from the in vitro COX inhibition assays.     

In vitro plant regeneration,phenolic compound production and pharmacological activities of Coleonema pulchellum

Effects of plant growth regulators (PGRs) and organic elicitors (OEs) on Coleonema pulchellum in vitro micropropagation, secondary product production and pharmacological activities were evaluated. In vitro, ex vitro and parental plants of C. pulchellum were investigated for their potential to produce phenolic and pharmacological compounds. Different morphogenic characteristics of shoots were obtained with PGRs- and OEs-containing media. A higher number of normal shoots were achieved with a low concentration of thidiazuron (TDZ: 4.5 μM). Lesser numbers were found with combinations of TDZ (13.6 μM) + indole-3-acetic acid (IAA: 2.9 μM); haemoglobin (HB: 300 mg l^− 1) or glutamine (GM: 40 μM) + benzyladenine (BA: 8.8 μM). Shoots were rooted in vitro and successfully acclimatized. Plant growth regulators and OEs had a significant effect on the synthesis and accumulation of phenolic compounds and flavonoids. In particular, casein hydrolysate (CH) as well as a combination of GM and BA induced high levels of total phenolics and flavonoids during in vitro culture. Cytokinins and OEs had a significant effect on DPPH radical scavenging and antibacterial activities of C. pulchellum extracts. Acclimatized C. pulchellum plants can be used as substitute alternative to natural populations.     

In vitro cytotoxicity and genotoxicity of five Ochna species (Ochnaceae) with excellent antibacterial activity

Extracts and fractions of some Ochna species had excellent antibacterial activity. Before considering the potential therapeutic use of these extracts it is important to determine the safety of extracts. The cytotoxicity of Ochna natalitia, Ochna pretoriensis, Ochna pulchra, Ochna gamostigmata, and Ochna serrulata (Ochnaceae) was determined in monkey kidney (Vero) cells, human hepatocellular carcinoma (C3A) cells and bovine dermis cells using the mitochondrial viability MTT assay. Their potential mutagenic effects were also determined using the Ames test with strains Salmonella typhimurium TA98 and TA100 with and without metabolic activation. The LC₅₀ values (the lethal concentration at which 50% of the cells are killed) of the extracts on the various cell lines ranged from 26 to 99 μg/ml. None of the plant species was mutagenic (mutagenic index values ≤ 1.59 for TA98 and ≤ 0.92 for TA100). In a previous study, we determined the antibacterial activity of the five extracts against Staphylococcus aureus, Escherichia coli, Enterococcus faecalis and Pseudomonas aeruginosa. From this we calculated the selectivity index (SI) values by dividing the LC₅₀ value by the minimum inhibitory concentration (MIC) to obtain the ratio of toxicity to bioactivity of each extract. The plant extracts had low SI values ≤ 1.307. This is a clear indication of non-selective toxicity, i.e. extracts are almost equally toxic to the bacteria and mammalian cell lines used in the assays. As a result, the extracts may have limited application as ingestible or intravenous therapeutic agents based on the in vitro findings. However, it may be necessary to also evaluate in vivo toxicity of the extracts in animal models as in vitro toxicity does not always equate to in vivo toxicity because of the difference in physiological microenvironment in live animals and tissue culture. Additionally, if it is the case that the toxic compounds are not the same as the active compounds, it may be possible to potentiate the extracts by the removal of toxic compounds and concentration of active compounds. The extracts may then be useful for development into treatments for topical bacterial infections.     

Design,synthesis and biological screening of some novel celecoxib and etoricoxib analogs with promising COX-2 selectivity,anti-inflammatory activity and gastric safety profile

Two new series of 4,6-diaryl-3-cyanopyridine 4a-r and 1,3,5-triaryl-2-pyrazolines 6a-f and were prepared. The new compounds were evaluated for their in vitro COX-2 selectivity and in vivo anti-inflammatory activity. Compounds 4o,r and 6d,f had moderate to high selectivity index (S.I.) compared to celecoxib (selectivity indexes of 4.5, 3.14, 4.79 and 3.21, respectively) and also, showed in vivo anti-inflammatory activity approximately equal to or higher than celecoxib (edema inhibition % = 60.5, 64.5, 59.3 and 59.3, after 3 h, respectively) and the effective anti-inflammatory doses were (ED₅₀ = 10.1, 7.8, 8.46 and 10.7 mg/kg respectively, celecoxib ED₅₀ = 10.8 mg/kg) and ulcerogenic liability were determined for these compounds which showed promising activity by being more potent than celecoxib with nearly negligible ulcerogenic liability compared to celecoxib (reduction in ulcerogenic liability versus celecoxib = 85, 82, 74 and 67%, respectively).     

Antimicrobial activities of Dilobeia thouarsii Roemer and Schulte,a traditional medicinal plant from Madagascar

The leaves of Dilobeia thouarsii (Roemer and Schulte), a tree that is endemic to Madagascar (Proteaceae), are used in traditional Malagasy medicine to treat bacterial skin infections and wounds. This study investigated the in vitro antibacterial activities of D. thouarsii leaf extracts and identified the bioactive compounds with the aim of providing a scientific basis for its use against skin diseases. Using broth microdilution method for leaf crude extract and its compounds, we investigated inhibition of the growth of Bacillus cereus, Bacillus megaterium, Staphylococcus aureus, Enterococcus faecalis, Vibrio harveyi, Vibrio fisheri, Salmonella Typhimurium, Salmonella antarctica, Escherichia coli, and Klebsiella pneumoniae. The two purified phenolic compounds from leaf ethyl acetate extracts (1, 2) were found to be more active than the crude extract itself. The structure of the two compounds was elucidated by NMR and mass spectrometry: compound 1 was identified as 4-aminophenol and compound 2 as 4-hydroxybenzaldehyde. A marked inhibitory effect (MIC < 0.1 mg/ml) was found against S. aureus, which is a major agent in skin infections. We observed moderate activities (MIC values of between 0.1 and 0.5 mg/ml) for E. faecalis, Vibrio spp., and Bacillus spp. Neither compound was active against Salmonella spp., E. coli and K. pneumoniae (MICs > 1 mg/ml). To conclude, the high antimicrobial activity of D. thouarsii leaf extracts against S. aureus supports its traditional use to treat skin infections.     

Impact of nutrients and herbivory by Eccritotarsus catarinensis on the biological control of water hyacinth,Eichhornia crassipes

Many water hyacinth infestations in South Africa are the symptom of eutrophication, and as a result, biological control of this weed is variable. This study examined the effects of herbivory by the mirid, Eccritotarsus catarinensis, on water hyacinth grown at high, medium and low nitrogen (N) and phosphorus (P) nutrient concentrations. Water nutrient concentration appears to be the overriding factor affecting plant growth parameters of water hyacinth plants—at high nutrient concentrations, leaf and daughter plant production were more than double than at low nutrient concentrations, while stem length was twice as great at high nutrient concentrations compared to low concentrations. Chlorophyll content was also twice as high at high nutrient concentrations than low concentrations. Conversely, flower production at high nutrient concentrations was less than half that at low concentrations. Herbivory by E. catarinensis did not have as great an effect on water hyacinth vigour as nutrient concentration did, although it significantly reduced the production of daughter plants by 23 ± 9%, the length of the second petiole by 13 ± 5%, and chlorophyll content of water hyacinth leaves by 15 ± 6%. In terms of insect numbers, mirids performed better on plants grown under medium nutrient conditions (99 ± 28 S.E.), compared to high nutrient concentrations (52 ± 27 S.E.), and low nutrient concentrations (25 ± 30 S.E.). Thus, these results suggest that the fastest and most significant reduction in water hyacinth proliferation would be reached by lowering the water nutrient concentrations, and herbivory by E. catarinensis alone is not sufficient to reduce all aspects of water hyacinth vigour, especially at very high nutrient concentrations.