Antibacterial profiling of abietane-type diterpenoids

Abietic and dehydroabietic acid are interesting diterpenes with a highly diverse repertoire of associated bioactivities. They have, among others, shown antibacterial and antifungal activity, potentially valuable in the struggle against the increasing antimicrobial resistance and imminent antibiotic shortage. In this paper, we describe the synthesis of a set of 9 abietic and dehydroabietic acid derivatives containing amino acid side chains and their in vitro antimicrobial profiling against a panel of human pathogenic microbial strains. Furthermore, their in vitro cytotoxicity against mammalian cells was evaluated. The experimental results showed that the most promising compound was 10 [methyl N-(abiet-8,11,13-trien-18-yl)-d-serinate], with an MIC₉₀ of 60 μg/mL against Staphylococcus aureus ATCC 25923, and 8 μg/mL against methicillin-resistant S. aureus, Staphylococcus epidermidis and Streptococcus mitis. The IC₅₀ value for compound 10 against Balb/c 3T3 cells was 45 μg/mL.     

Psychopharmacological profile of Chamomile (Matricaria recutita L.) essential oil in mice

In this study, the effect of Matricaria recutita L. essential oil (MEO) on the central nervous system (CNS) of mice was investigated using some behavioral methods. Chemical profiling both by GC and GC-MS analyses of the hydrodistilled essential oil of M. recutita revealed α-bisabolol oxide A (28%), α-bisabolol oxide B (17.1%), (Z)-β-Farnesene (15.9%) and α-bisabolol (6.8%) as the main components. Changes induced by MEO (25, 50 and 100 mg/kg) and reference drug caffeine (25 mg/kg) in spontaneous locomotor activities and motor coordinations of mice were investigated by activity cage measurements and Rota-Rod tests, respectively. Open field, social interaction and elevated plus-maze tests were applied to assess the emotional state of the animals. Further, tail-suspension test was performed for evaluating the effect of MEO on depression levels of mice. As a result, at 50 and 100 mg/kg, MEO significantly increased the numbers of spontaneous locomotor activities, exhibited anxiogenic effect in the open field, elevated plus-maze and social interaction tests and decreased the immobility times of animals in tail suspension tests. The falling latencies in Rota-Rod tests did not change. This activity profile of MEO was similar to the typical psychostimulant caffeine. The exact mechanism of action underlying this stimulant-like effect should be clarified with further detailed studies.     

Effects of orlistat and its relationship with nitric oxide in the small intestinal mucosa

Nitric oxide (NO) is known to be a messenger molecule that plays an important role in physiological and pathological conditions. It is synthesized by an enzyme called nitric oxide synthase (NOS). Inducible NOS (iNOS), one of the three isomers of NOS, has both protective and toxic properties. In this study, the role of NO has been evaluated by gastrointestinal symptoms induced by orlistat which is used in obesity treatment. Orlistat was given to Wistar rats with and without iNOS inhibition. The effects of orlistat and inhibition of NOS were studied. Glucose, urea, alanine transaminase (ALT), and gamma glutamil transpeptidase (GGT) were descreased after short- and long- term orlistat applications. Dexamethasone increased level of these enzymes. Cholesterol and triglyceride were increased in all experimental groups than the controls. This increment was more severe in animals received orlistat and dexamethasone together. Small intestinal tissue also were researched histologically and NADPH-diaphorase (NADPH-d) histochemistrically. Orlistat caused histological damages in brush border membranes, connective tissues of villi, and lymphocyte migration also increased. Dexamethasone treatment prevented these damages partially while orlistat increased the NOS distribution in the tissue sections. Dexamethasone, which is an iNOS inhibitor, decreased NADPH-d histochemistry. There was a similiar NOS distribution both in the control and orlistat+dexamethasone group. Hence, we concluded that long- term trials with orlistat and similar drugs are needed.     

Synthesis,structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one‐pot synthesis method. The structures were characterized by elemental analysis, IR, ¹H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single‐crystal X‐ray diffraction. The findings showed that the metal atom adopts a slightly distorted square‐pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake‐flask method, another pharmacokinetic parameter. The findings showed that the IC ₅₀ values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.     

Strain and plastic composite support (PCS) selection for vitamin K (Menaquinone-7) production in biofilm reactors

Menaquinone-7 (MK-7), a subtype of vitamin K, has received a significant attention due to its effect on improving bone and cardiovascular health. Current fermentation strategies, which involve static fermentation without aeration or agitation, are associated with low productivity and scale-up issues and hardly justify the commercial production needs of this vitamin. Previous studies indicate that static fermentation is associated with pellicle and biofilm formations, which are critical for MK-7 secretion while posing significant operational issues. Therefore, the present study is undertaken to evaluate the possibility of using a biofilm reactor as a new strategy for MK-7 fermentation. Bacillus species, namely, Bacillus subtilis natto, Bacillus licheniformis, and Bacillus amyloliquifaciens as well as plastic composite, supports (PCS) were investigated in terms of MK-7 production and biofilm formation. Results show the possibility of using a biofilm reactor for MK-7 biosynthesis. Bacillus subtilis natto and soybean flour yeast extract PCS in glucose medium were found as the most potent combination for production of MK-7 as high as 35.5 mg/L, which includes both intracellular and extracellular MK-7.     

Recognition of ribosomal protein L11 by the protein trimethyltransferase PrmA

Bacterial ribosomal protein L11 is post-translationally trimethylated at multiple residues by a single methyltransferase, PrmA. Here, we describe four structures of PrmA from the extreme thermophile Thermus thermophilus. Two apo-PrmA structures at 1.59 and 2.3 A resolution and a third with bound cofactor S-adenosyl-L-methionine at 1.75 A each exhibit distinct relative positions of the substrate recognition and catalytic domains, revealing how PrmA can position the L11 substrate for multiple, consecutive side-chain methylation reactions. The fourth structure, the PrmA-L11 enzyme-substrate complex at 2.4 A resolution, illustrates the highly specific interaction of the N-terminal domain with its substrate and places Lys39 in the PrmA active site. The presence of a unique flexible loop in the cofactor-binding site suggests how exchange of AdoMet with the reaction product S-adenosyl-L-homocysteine can occur without necessitating the dissociation of PrmA from L11. Finally, the mode of interaction of PrmA with L11 explains its observed preference for L11 as substrate before its assembly into the 50S ribosomal subunit.     

Advances in biofilm reactors for production of value-added products

Biofilms are defined as microbial cell layers, which are irreversibly or reversibly attached on solid surfaces. These attached cells are embedded in a self-produced exopolysaccharide matrix, and exhibit different growth and bioactivity compared with suspended cells. With their high biomass density, stability, and potential for long-term fermentation, biofilm reactors are employed for the fermentation and bioconversion, which need large amount of biomass. During the past decade, biofilm reactors have been successfully applied for production of many value-added products. This review article summarizes the applications of biofilm reactors with different novel designs. Advantages and concerns using biofilm reactors, potential uses for industrial-scale production, and further investigation needs are discussed.     

Salt Stress Mitigating Potential of Halotolerant/Halophilic Plant Growth Promoting

Abstract

In the current study, the PGP (production of siderophore and IAA, fixation of nitrogen and solubilization of phosphate) potential of forty-five bacterial isolates comprising sixteen genera (Marinibacillus, Zhihengliuella, Bacillus, Nesterenkonia, Halobacillus, Promicromonospora, Terribacillus, Jeotgalibacillus, Staphylococcus, Oceanobacillus, Virgibacillus, Halomonas, Gracilibacillus, Planococcus, Thalassobacillus and Microbacterium) was investigated. Among these forty-five bacterial isolates, most of the isolates (40 isolates) possess plant growth promoting potential. Four bacterial isolates [Marinibacillus sp. (EM1), Zhihengliuella salsuginis (EM30), Planococcus sp. (EK9), and Promicromonospora sp. (EK12)] possessing PGP traits were applied on the barley grown under salt (NaCl) stress in a hydroponic system. Comparing to the un-inoculated group, all the four bacterial isolates significantly improved plant growth that inhibited with NaCl (200?mM) stress. The growth rate of the plants inoculated with Zhihengliuella salsuginis (EM30), Promicromonospora sp. (EK12), Planococcus sp. (EK9), and Marinibacillus sp. (EM1) was 81.86, 80.51, 70.62 and 69.22, respectively. As far as we know, this is the first report showing the PGP potential of Marinibacillus sp. (EM1), Bacillus horikoshii (EM9), Bacillus patagoniensis (EM12), Bacillus agaradhaerens (EK13), Oceanobacillus profundus (EM26) Thalassobacillus devorans (EM34) and Promicromonospora sp. (EK12).