Isolation and characterization of phthalates from Brevibacterium mcbrellneri that cause cytotoxicity and cell cycle arrest

Bacteria belonging to the family Brevibacterieae are ubiquitous Gram positive organisms that are responsible for the feet odour and cheese aroma. Brevibacterium mcbrellneri is a relatively new member belonging to Brevibac- terieae. In the current manuscript we discuss isolation of biologically active metabolites from Brevibacterium mcbrellneri. Two aromatic esters were isolated from Brevibacterium mcbrellneri by “Bioassay guided fractiona- tion strategy” and identified as di-(2-ethylhexyl) phthalate and dibutyl phthalate by chemical characterization using biophysical techniques. The phthalate compounds show broad spectrum antibacterial activity and mosquito larvi-cidal activity. Mosquito larvicidal activity has been attributed to inhibition of acetylcholinesterase enzyme activity. These compounds were found to be cytotoxic in multiple cell lines causing cell cycle arrest in G1 phase

Phytofabrication of silver nanoparticles using Myriostachya wightiana as a novel bioresource, and evaluation of their biological activities

ABSTRACT Nanobiotechnology deals with the properties of nanomaterials and their potential uses. Here we report for the first time novel, cost-effective and eco-friendly method for the rapid green synthesis of silver nanoparticles (AgNPs) using leaf extracts of Myriostachya wightiana. The growth of silver nanoparticles was monitored by UV-vis spectroscopy complemented by Zeta potential, dynamic light scattering technique (DLS), Fourier-transform infrared spectroscopy (FTIR), Transmission electron microscope (TEM) and X-ray diffraction (XRD). The surface plasmon resonance (SPR) band found at 434 nm confirmed the reduction of AgNO3 to AgNPs. TEM micrographs revealed that AgNPs are irregular in shape with the size range from 15-65 nm. The functional groups responsible for bio-reduction of silver nitrate into silver were analyzed by FTIR and confirmed by X-ray photoelectron spectrum (XPS). Further these biogenic AgNP were evaluated for insecticidal activities against stored product pests, Tribolium castaneum (Flour beetle), Rhyzopertha dominica (F.)(Lesser grain borer) and Sitophilus oryzae L (Rice weevil). The fabricated AgNPs showed moderate activity on stored pests and strong antibacterial activity with varying degrees against Xanthomonas campestris and Ralstonia solanacearum as evidenced by their zone of inhibition at all concentrations. Hence, these AgNP can be used as control agents against agricultural pests and pathogens in future

Endophytic Fungi as Novel Resources of natural Therapeutics

ABSTRACT Fungal endophytes constitute a major part of the unexplored fungal diversity. Endophytic fungi (EF) are an important source for novel, potential and active metabolites. Plant-endophyte interaction and endophyte -endophyte interactions study provide insights into mutualism and metabolite production by fungi. Bioactive compounds produced by endophytes main function are helping the host plants to resist external biotic and abiotic stress, which benefit the host survival in return. These organisms mainly consist of members of the Ascomycota, Basidiomycota, Zygomycota and Oomycota. Recently, the genome sequencing technology has emerged as one of the most efficient tools that can provide whole information of a genome in a small period of time. Endophytes are fertile ground for drug discovery. EFare considered as the hidden members of the microbial world and represent an underutilized resource for new therapeutics and compounds. Endophytes are rich source of natural products displaying broad spectrum of biological activities like anticancer, antibacterial, antiviral, immunomodulatory, antidiabetic, antioxidant, anti-arthritis and anti-inflammatory

Bruton's tyrosine kinase associates with the actin-based cytoskeleton in activated platelets

Bruton's tyrosine kinase (Btk) plays a crucial role in the maturation and differentiation of B-lymphocytes and immunoglobulin synthesis. Recently Btk has been described to be present in significant amount in human platelets. To investigate the regulation of this kinase in the platelets we studied its subcellular redistribution in the resting and activated cells. In the resting platelets Btk was almost absent from the actin-based cytoskeleton. Upon challenge of the platelet thrombin receptor upto 30% of total Btk appeared in the cytoskeleton and the protein underwent phosphorylation on tyrosine. Translocation of Btk to the cytoskeleton but not aggregation was prevented by cytochalasin B, which inhibits actin polymerization. Wortmannin and genistein (inhibitors of phosphoinositide 3-kinase and protein tyrosine kinase, respectively) decreased while phenylarsine oxide (a tyrosine phosphatase inhibitor) increased the cytoskeletal content of Btk. The association of Btk with the cytoskeleton was regulated by integrin α<SUB>IIb</SUB>β<SUB>3</SUB> and partly reversible. Taken together, these data suggest that Btk might be a component of a signaling complex containing specific cytoskeletal proteins in the activated platelets. J. Cell. Biochem. 81: 659–665, 2001. © 2001 Wiley-Liss, Inc

Regulation of postaggregation events induced by protease-activated receptor 1 ligation in human platelets: evidence of differential signaling pathways

In a physiological milieu platelets continue to be exposed to agonists long after clot formation. We studied the regulation of postaggregation events consequent on protease-activated receptor (PAR) 1 ligation with either thrombin or the thrombin receptor-activating peptide (TRAP). Stimulation with TRAP (20 μM) but not with thrombin (1 U/ml) for 15 min evoked platelet disaggregation by about 30% and downregulation of high-affinity fibrinogen binding sites on integrin αIIbβ3 to nearly prestimulation levels. Concurrently, only TRAP disorganized the actin-based cytoskeleton, with decrease in the cytoskeletal content of focal contact-associated proteins like integrin αIIbβ3, Src, and focal adhesion kinase (FAK). While protein tyrosine kinases were activated during the initial period of platelet aggregation with either agonist, stimulation of protein tyrosine phosphatases determined the successive phase of reduced phosphotyrosine content. SHP-1, an abundant protein tyrosine phosphatase in the platelets, was tyrosine phosphorylated on challenge of PAR-1 and coprecipitated with two unidentified tyrosine phosphorylated proteins of 140 and 60 kDa; in addition, SHP-1 tyrosine phosphorylation (which is associated with enhanced phosphatase activity) was sustained until 15 min. Activity of calpain was upregulated following incubation with thrombin and not with TRAP. Collectively, these data suggest that signaling pathways elicited by PAR-1 agonists thrombin and TRAP are markedly different, which could have important implications on late platelet responses

Synthesis, glycosidase inhibitory activity and computational studies of dideoxymethylnojirimycin and its derivatives

We report here the synthesis and biological evaluation of dideoxynojirimycin and its analogs and their functional effect on glucosidase enzyme inhibition against α-glucosidase(yeast), α-galactosidase and β-galactosidase (kluyveromyces lactis). All the compounds significantly inhibited the α-glucosidase(yeast) activity when compared to DNJ and shown strong inhibition against β-galactosidase (kluyveromyces lactis) when compared to DNJ. The molecular docking studies also reveals that these compounds showing strong ligand binding energies against yeast-ɑ-glucosidase- I, yeast β-galactosidase and human lysosomal acid–ɑ-glucosidase. Interestingly the analogues having N-H, N-alkyl and N-benzyl group along with ethyl group significantly inhibited the β-galactosidase activity when compared to DNJ. The in-silico studies are in correlation with invitro activity data; therefore, this study will be useful to develop further glycosidase inhibitors