Design and synthesis of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones as a novel class of analgesic and anti-inflammatory agents

A new series of 3-(4-ethylphenyl)-2-substituted amino-3H-quinazolin-4-ones were synthesized by reacting the amino group of 2-hydrazino-3-(4-ethylphenyl)-3H-quinazolin-4-one from 4-ethyl aniline with a variety of aldehydes and ketones. The title compounds were investigated for analgesic, anti-inflammatory and ulcerogenic index activities. The compound 2-(N'-3-pentylidene-hydrazino)-3-(4-ethylphenyl)-3H-quinazolin-4-one (AS2) emerged as the most active compound of the series and was moderately more potent than the reference standard diclofenac sodium. Interestingly the test compounds showed only mild ulcerogenic potential when compared to aspirin.     

Wnt signaling in kidney development and disease

The Wnt gene family, which encodes secreted growth and differentiation factors, has been implicated in kidney organogenesis. The Wnts control both ureteric bud development and signaling, but they also serve as inductive factors to regulate nephrogenesis in the mesenchcymal cells. Several of the Wnt genes are expressed in the developing kidney, and gene knock-out studies have revealed specific developmental functions for these. Consistent with this, changes in Wnt ligands and pathway components are associated with many kidney diseases, including kidney cancers, renal fibrosis, cystic kidney diseases, acute renal failure, diabetic nephropathy and ischaemic injury. It is these associations of the Wnt signaling system with kidney development and kidney diseases that form to topic of this review.Key words: Wnt signaling, tubule induction, ureter development, kidney diseases, kidney cancer     

Synthesis and antibacterial activity of novel oxazolidinones bearing N-hydroxyacetamidine substituent

Novel oxazolidinone antibacterials containing N-hydroxyacetamidine moiety are synthesized with the diversity at C-5 terminus. These compounds have been evaluated against a panel of clinically relevant gram-positive and gram-negative pathogens. Most of the analogs in this series displayed activity superior to Linezolid and in vivo efficacies of selected oxazolidinones are also disclosed herein.     

Use of plant products and copepods for control of the dengue vector, <Emphasis Type="Italic">Aedes aegypti</Emphasis>

The efficacy of plant extracts (neem tree, Azadirachta indica A. Juss.; Meliaceae) and copepods [Mesocyclops aspericornis (Daday)] for the control of the dengue vector Aedes aegypti L. was tested in the laboratory. Neem Seed Kernel Extract (NSKE) at 25, 50, 100, 200 and 400 ppm caused significant mortality of Ae. aegypti larvae. Lethal concentrations (LC₅₀ and LC₉₀) were worked out. The LC₅₀ and LC₉₀ values for I to IV larval instars were 111.98, 138.34, 158.93, 185.22 ppm and for pupae was 146.13 ppm, respectively. The LC₉₀ value of I instar was 372.95 ppm, II instar was 422.77 ppm, III instar was 440.63 ppm, IV instar was 456.96 ppm, and pupae was 476.92 ppm, respectively. A study was conducted to test the whether the predatory efficiency of copepods on first instars changed in the presence of NSKE. The percentage of predatory efficiency of copepod was 6.80% in treatments without NSKE and the percentage of predatory efficiency increased up to 8.40% when copepods were combined with NSKE. This increase in predation efficiency may caused by detrimental effects of the neem active principle compound (Azadirachtin) on the mosquito larvae. Our results suggest that the combined application of copepods and neem extract to control Aedes populations is feasible. Repeated application of neem does not cause changes in copepod populations, because neem is highly degradable in the environment.     

Selection pressure required for long-term persistence of blaCMY-2-positive IncA/C plasmids

Multidrug resistance blaCMY-2 plasmids that confer resistance to expanded-spectrum cephalosporins have been found in multiple bacterial species collected from different hosts worldwide. The widespread distribution of blaCMY-2 plasmids may be driven by antibiotic use that selects for the dissemination and persistence of these plasmids. Alternatively, these plasmids may persist and spread in bacterial populations in the absence of selection pressure if a balance exists among conjugative transfer, segregation loss during cell division, and fitness cost to the host. We conducted a series of experiments (both in vivo and in vitro) to study these mechanisms for three blaCMY-2 plasmids, peH4H, pAR060302, and pAM04528. Results of filter mating experiments showed that the conjugation efficiency of blaCMY-2 plasmids is variable, from <10(-7) for pAM04528 and peH4H to ～10(-3) for pAR060302. Neither peH4H nor pAM04528 was transferred from Escherichia coli strain DH10B, but peH4H was apparently mobilized by the coresident trimethoprim resistance-encoding plasmid pTmpR. Competition studies showed that carriage of blaCMY-2 plasmids imposed a measurable fitness cost on the host bacteria both in vitro (0.095 to 0.25) and in vivo (dairy calf model). Long-term passage experiments in the absence of antibiotics demonstrated that plasmids with limited antibiotic resistance phenotypes arose, but eventually drug-sensitive, plasmid-free clones dominated the populations. Given that plasmid decay or loss is inevitable, we infer that some level of selection is required for the long-term persistence of blaCMY-2 plasmids in bacterial populations.     

Insights into the binding specificity of wild type and mutated wheat germ agglutinin towards Neu5Acα(2‐3)Gal: a study by in silico mutations and molecular dynamics simulations

Wheat germ agglutinin (WGA) is a plant lectin, which specifically recognizes the sugars NeuNAc and GlcNAc. Mutated WGA with enhanced binding specificity can be used as biomarkers for cancer. In silico mutations are performed at the active site of WGA to enhance the binding specificity towards sialylglycans, and molecular dynamics simulations of 20 ns are carried out for wild type and mutated WGAs (WGA1, WGA2, and WGA3) in complex with sialylgalactose to examine the change in binding specificity. MD simulations reveal the change in binding specificity of wild type and mutated WGAs towards sialylgalactose and bound conformational flexibility of sialylgalactose. The mutated polar amino acid residues Asn114 (S114N), Lys118 (G118K), and Arg118 (G118R) make direct and water mediated hydrogen bonds and hydrophobic interactions with sialylgalactose. An analysis of possible hydrogen bonds, hydrophobic interactions, total pair wise interaction energy between active site residues and sialylgalactose and MM‐PBSA free energy calculation reveals the plausible binding modes and the role of water in stabilizing different binding modes. An interesting observation is that the binding specificity of mutated WGAs (cyborg lectin) towards sialylgalactose is found to be higher in double point mutation (WGA3). One of the substituted residues Arg118 plays a crucial role in sugar binding. Based on the interactions and energy calculations, it is concluded that the order of binding specificity of WGAs towards sialylgalactose is WGA3 > WGA1 > WGA2 > WGA. On comparing with the wild type, double point mutated WGA (WGA3) exhibits increased specificity towards sialylgalactose, and thus, it can be effectively used in targeted drug delivery and as biological cell marker in cancer therapeutics. Copyright © 2014 John Wiley & Sons, Ltd.     

Fermentative production of dextran using Leuconostoc spp. isolated from fermented food products

Leuconostoc spp. （LSland LI1） isolated from sauerkraut and idli batter was selected for dextran production. To enhance the yield of dextran, effects of various parameters such as sucrose concentration, pH, temperature, incubation and inoculum percentage were analyzed. The optimum sucrose concentration for the Leuconostoc spp. （LS1 and LI1） was found to be 15% and 25% respectively. Isolates produced maximum dextran after 20 h of incubation at 29℃ and the optimum pH was found between 8 and 8.5. The inoculum concentration of 7.5% was more favorable for the production of dextran by Leuconostoc spp. （LS1 and LI1）. The growth kinetic parameters were studied and compared for the strains LS1 and LI1. Mass production of dextran was carried out using a stirred tank batch reactor. FTIR analysis was done to determine the functional groups of dextran, sephadex is prepared by cross linking dextran using epichlorohydrin and the functional groups are determined by FTIR analysis.     

Surface functionalization of nanobiomaterials for application in stem cell culture,tissue engineering,and regenerative medicine

Stem cell‐based approaches offer great application potential in tissue engineering and regenerative medicine owing to their ability of sensing the microenvironment and respond accordingly (dynamic behavior). Recently, the combination of nanobiomaterials with stem cells has paved a great way for further exploration. Nanobiomaterials with engineered surfaces could mimic the native microenvironment to which the seeded stem cells could adhere and migrate. Surface functionalized nanobiomaterial‐based scaffolds could then be used to regulate or control the cellular functions to culture stem cells and regenerate damaged tissues or organs. Therefore, controlling the interactions between nanobiomaterials and stem cells is a critical factor. However, surface functionalization or modification techniques has provided an alternative approach for tailoring the nanobiomaterials surface in accordance to the physiological surrounding of a living cells; thereby, enhancing the structural and functional properties of the engineered tissues and organs. Currently, there are a variety of methods and technologies available to modify the surface of biomaterials according to the specific cell or tissue properties to be regenerated. This review highlights the trends in surface modification techniques for nanobiomaterials and the biological relevance in stem cell‐based tissue engineering and regenerative medicine. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:554–567, 2016     

Phytoremediation potential of some agricultural plants on heavy metal contaminated mine waste soils,salem district,tamilnadu

The Pot culture experiment performed for phytoextraction potential of selected agricultural plants [millet (Eleusine coracana), mustard (Brassica juncea), jowar (Sorghum bicolor), black gram (Vigna mungo), pumpkin (Telfairia occidentalis)] grown in metal contaminated soils around the Salem region, Tamilnadu, India. Physiochemical characterization of soils, reported as low to medium level of N, P, K was found in test soils. The Cr content higher in mine soils than control and the values are 0.176 mg/L in Dalmia soil and 0.049 mg/L in Burn &; Co soil. The germination rate low in mine soil than control soils (25 to 85%). The content of chlorophyll, carotenoid, carbohydrate and protein decreased in mine soils than control. The morphological parameters and biomass values decreased in experimental plants due to metal accumulation. Proline content increased in test plants and ranged from 0.113 mg g^?1 to 0.858 mg g^?1 which indicate the stress condition due to toxicity of metals. Sorghum and black gram plants reported as metal tolerant capacity. Among the plants, Sorghum produced good results (both biomass and biochemical parameters) which equal to control plant and suggests Sorghum plant is an ideal for remediation of metal contaminated soils.