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With an aim to construct novel anticancer drugs, a series of polycyclic heterocycles comprising diverse structural sub-units based on molecular hybridization strategy have been designed and synthesized through a three-component [3 + 2]-cycloaddition/annulation strategy. Anticancer evaluation of these compounds against MCF-7 and NCI-H460 cell lines revealed dose dependent reduction with noteworthy anticancer activity. Compound 4b inhibited MCF-7 and NCI-H460 cell lines with IC50 values 10.86 ± 0.94 and 9.17 ± 0.63 µM respectively. Further, apoptosis and cell cycle analysis revealed that this compound was able to prompt apoptosis at an early stage in MCF-7 cell line besides increasing the threshold of MMP and % of cells expressing FITC-dUTP. These results suggest that compound 4b is a potential molecule for the further exploration.

A three‐component, [3 + 2]‐cycloaddition/annulation domino protocol is described for the synthesis in excellent yield of a polycyclic cage‐like heterocyclic hybrid (PCHH) that comprises various advantaged structural units viz., α,β‐unsaturated ketone moiety, 4‐pyridinone and pyrroloisoquinoline in a cage‐like framework. The antitumor activity of PCHH on human breast (MCF7), colon (HCT116), cervical (JURKAT) and lung (NCI‐H460) malignant cell lines inhibited the propagation of all cell lines. This hybrid molecule displayed increased broad‐spectrum anticancer activity with higher doses of PCHH. Furthermore, the compound induced 45.21% of early apoptosis and 46.32% of late apoptosis in the Jurkat cancer cell line. Cell cycle analysis showed that this cage‐like compound caused cell cycle arrest of Jurkat cells at the S phase and sub G0/G1 phase. Additionally, it led to increased DNA fragmentation and mitochondrial membrane permeabilization through activation of caspase‐3 enzyme. Present investigation demonstrates the specific cytotoxic activity of the cage‐like compound and the induction of apoptosis through the intrinsic pathway of Jurkat cells. [ABSTRACT FROM AUTHOR]

Two series of dimethoxyindanone imbedded novel fluorinated spiropyrrolidine heterocyclic hybrids were synthesized employing two different less explored azomethine ylides and were measured for their efficiency as inhibitors for Alzheimer's disease. Among the spiropyrrolidine heterocyclic hybrids, the indole based fluorinated compound with a methoxy substituent at the meta- position of the aryl ring exhibited the utmost potent AChE and BChE inhibitory activities with an IC 50 of 1.97 ± 0.19 µM and 7.08 ± 0.20 µM respectively. The plausible mechanism of inhibition on ChE receptors was unveiled via molecular docking studies. [ABSTRACT FROM AUTHOR]

A small library of cage-like heterocyclic hybrids encompassing pyrroloisoquinolines, pyridinone and acenaphthene structural moieties have been synthesized and tested for their potential as anticancer agents against HCT116 and JURKAT cell lines. The results revealed that these cell lines are more sensitive towards compound 1g and it showed dose dependent cytotoxic effect at 48 hrs of incubation. The IC 50 values of compound 1g against HCT116 and JURKAT cell lines are 12.14 ± 1.53 and 10.68 ± 0.68 µM, respectively. Further studies on the determination of mechanism of action of compound 1g discovered that it brought the cell death by inducing Caspase 3 dependent apoptosis and also by arresting the cell cycle at S phase. These studies revealed that compound 1g can be recommended as a potential anti-cancer agent. [ABSTRACT FROM AUTHOR]

Byline: Sudhir. Patil, T. Prakash, D. Kotresha, N. Rao, Naitik. Pandy Objective : To study the antihyperlipidemic effect of Cedrus deodara (C. deodara) against monosodium glutamate (MSG) induced obesity in [...]

Pseudomonas aeruginosa MTCC 4997 capable of degrading phenol was isolated and its immobilization potential in calcium alginate, polyurethane foam, k-carrageenan, polyacrylamid, agarose and hen egg white was investigated. All the immobilized matrices showed faster degradation than free cells in a packed bed reactor. Comparatively polyurethane foam immobilized cells retained 100% phenol degradation recorded up to150 mL/h flow rate followed by 50 mL/h flow rate from alginate and k-carrageenan, respectively. Furthermore, polyurethane foam immobilized cells capable of degrading phenol up to the concentration of 1500 mg/L with in 750 min. Polyurethane foam immobilized non-regenerated and regenerated cells were tested for their phenol degradability up to 150 days. Non-regenerated cells showed 100% efficiency of phenol degradation up to 90 days, while regenerated cells showed significant100% efficiency up to 135 days. [ABSTRACT FROM AUTHOR]

The aim of the current study was to isolate and characterize a strain which could utilize catechol as sole source of carbon and energy. The strain Achromobacter xylosoxidans 15DKVB was isolated from paper and pulp industrial effluent contaminated site of Harihar. In the present study 38 bacterial strains isolated were investigated for their ability to degrade catechol in MBM at different concentrations ranging from 100 mg/L to 2000 mg/L. The taxonomic position of strain 15DKVB was studied by sequencing of 16SrRNA gene with a GenBank accession number HQ448950. The maximum-likelihood algorithm showed that, strain 15DKVB formed a coherent cluster with the clade that comprised type strains of Achromobacter genus. The optimal temperature and pH for biodegradation of catechol by strain 15DKVB were 37 °C and pH 7.5 respectively. Among the carbon and nitrogen sources tested, glucose (83.4%) and yeast extract (99.6%) showed highest catechol degradation. Interestingly the strain 15DKVB was able to degrade catechol completely up to 1600 mg/L within 198 h. Immobilization experiment demonstrated that freely suspended cells could degrade 500 mg/L catechol within 60 h of incubation, whereas, the same cell population in alginate-immobilized flask, amended with 500 mg/L catechol was degraded in 42 h. Our results evidently depict that physicochemical parameters of Harihar industrial effluents does not comply with national standards set by ISI to discharge the effluents into irrigation waters. The isolated strain 15DKVB could be a good alternative for the bioremediation of catechol contaminated paper and pulp industrial effluent water and soil. These findings may open new bioremediation applications for the degradation of catechol. [ABSTRACT FROM AUTHOR]

Context: Terminalia chebula Retz. (Combretaceae) is a medium-sized tree that grows in the wild throughout India. T. chebula has been extensively used in Ayurveda, Unani, and homoeopathic medicine. The fruit has been used as a traditional medicine for a household remedy against various human ailments. Traditionally T. chebula is used to cure chronic ulcer, gastritis, and stomach cancers. Objective: The present study is to evaluate the antiulcer effect of hydroalcoholic (70%) extract of Terminalia chebula fruit. Materials and methods: Aspirin, ethanol and cold restraint stress-induced ulcer methods in rats were used for the study. The effects of the extract on gastric secretions, pH, total and free acidity using pylorus ligated methods were also evaluated. Results: Animals pretreated with doses of 200 and 500 mg/kg hydroalcoholic extract showed significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (P < 0.05 and P < 0.01) in the aspirin, ethanol and cold restraint stress-induced ulcer models. Similarly extracts increased mucus production in aspirin and ethanol-induced ulcer models. At doses of 200 and 500 mg/kg of T. chebula extract showed antisecretory activity in pylorus ligated model, which lead to a reduction in the gastric juice volume, free acidity, total acidity, and significantly increased gastric pH. Discussion and conclusion: These findings indicate that hydroalcoholic extract of the fruit T. chebula displays potential antiulcerogenic activity. This activity thus lends pharmacological credence to the suggested use of the plant as a natural remedy in the treatment or management of ulcer. [ABSTRACT FROM AUTHOR]

A small library of new class of dispiropyrrolidinyl-piperidone tethered indono[1,2- b ]quinoxaline heterocyclic hybrids 7 a – j were synthesized employing multicomponent 1,3-dipolar cycloaddition strategy in [bmim]Br. The azomethine ylide employed is first of its kind and generated in situ from indenoquinoxalinone and l -tryptophan, a combination that has not been employed previously for the in situ generation of azomethine ylides. The synthesized heterocyclic hybrids 7a – j were evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, therein compounds 7h and 7j displayed more potent AChE and BChE enzyme inhibition than the standard drug with IC 50 values of 3.22, 2.01, 12.40 and 10.45 mM, respectively. Molecular docking studies have also been investigated for most active compounds that disclosed interesting binding templates to the active site channel of cholinesterase enzyme. [ABSTRACT FROM AUTHOR]

A small library of spirooxindole-pyrrolidine hybrids have been synthesized for the first time in an ionic liquid, [bmim]Br in good to excellent yields employing a new class of non-stabilized azomethine ylides derived from isatin and tyrosine, a combination that has been rarely employed for the in situ generation of azomethine ylides using [3+2] cycloaddition strategy. Following the synthesis and characterization of the spirooxindole-pyrrolidine heterocyclic hybrids, they were tested for their anticancer activity as against the changes in the concentrations and time periods with different in vitro cell cultures containing cancer and non-cancer cells, where the results revealed for a potential therapeutic activity. Further analysis for the mechanism of cell death by the cancer cells indicated for the caspase-dependent apoptotic pathway, specifically mediated by caspase-3. Based on these results, it can be demonstrated that the synthesized spirooxindole-pyrrolidine hybrids may serve as one of the better therapeutic agents used for the treatment of malignant tumors. [ABSTRACT FROM AUTHOR]

Graphical abstract Highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields and assessed for their potential as inhibitors of AD. Compound bearing nitro groups on both the aryl rings showed the highest activity and this is also supported by its inhibition mechanisms on AChE and BChE receptors. Highlights • Novel highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields. • The structure of 4 H -pyrans were confirmed by FT-IR and NMR spectroscopic studies. • The compounds were evaluated as potential agents for Alzheimer's disease. • Molecular docking simulation was performed to disclose the mechanism of inhibition. Abstract Novel highly functionalized 2-amino-4 H -pyrans were achieved in excellent yields under simple grinding at ambient temperature and were assessed for their potential for treating Alzheimer's disease (AD). The 2-amino-4 H -pyran bearing nitro groups on both the aryl rings showed the highest activity, with an IC 50 of 1.98 ± 0.09 µM against acetylcholinesterase (AChE) and 10.62 ± 0.21 µM against butyrylcholinesterase (BChE), the inhibition mechanisms on AChE and BChE receptors were revealed by means of molecular docking simulations. [ABSTRACT FROM AUTHOR]

A regio and stereo- selective synthesis of hitherto unexplored hybrid heterocyclic system comprising spiropyrrolidine, indolizino[6,7- b ]indole units in good to excellent yields, has been developed via three component 1,3-dipolar cycloaddition and concomitant trifluoroacetic acid catalyzed Pictet-Spengler cyclization with paraformaldehyde. The newly synthesized compounds were evaluated for their in vitro acetylcholinesterase (AChE) and butylcholinesterase (BChE) enzyme inhibitory activities. Most of the synthesized compounds showed good inhibitory activity, among them, compounds 4d and 4g displayed highest potency against AChE (IC 50 1.88 and 1.98 μM), and BChE (IC 50 18.32 and 10.21 μM) enzyme, respectively than the standard drug, galanthamine. Molecular modeling simulation was investigated for the most active compounds 4d and 4g on AChE and BChE enzymes to disclose the binding and orientation of these molecules into active site of respective receptors. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Oxidative stress has been involved in the pathogenesis of several neurological diseases including acute stroke.Focal and global cerebral ischemia represents diseases that are common in the human population.In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke.Possible effect of a hydroalcoholic leaf extract of Clerodendron glandulosum Coleb ( C. glandulosum )on oxidant-antioxidant status in ischemia-hypoperfusion injury in the rat forebrain has been investigated.Healthy adult male Wistar albino rats were divided into five groups ( n = 8). Group I was served as Sham control (normal saline 1 ml/kg, orally), group II was served hypoperfusion control (normal saline 1 ml/kg, orally), group III, group IV were served as hydroalcoholic extract treated (200 and 400 mg/kg, orally) and group V was treated with Quercetin (10 mg/kg, orally) for 14 days to assess preventive and curative effects of C. glandulosum . Flavonoid and phenolic compounds exhibit a broad spectrum of biological activity, including antioxidant. C. glandulosum extract (200 and 400 mg/kg, p.o) was administered orally, once daily for a period of 2 weeks after the occlusion of BCCA. After 14th days rats were subjected to behavioral studies. After behavioral studies animals were sacrificed and brain was removed and homogenized. Estimation of Lipid peroxidation (LPO) Myeloperoxidase (MPO), estimation of protein levels and the activities of Superoxide dismutase (SOD), Catalase (CAT), were performed. Infarct size and histopathological changes were observed in treated groups. [ABSTRACT FROM AUTHOR]

Toxoplasmosis is an important cause of congenital infection. The present study was performed to evaluate the usefulness of recombinant (r) GRA-7 cloned from nucleotides (n) 39-711 in discriminating between acute and chronic toxoplasmosis. First, commercial IgM, IgG and IgG avidity ELISAs were used to determine the serological profile of the sera. Serum samples were from 20 symptomatic patients with acute infection (low IgG avidity, IgM positive), 10 with chronic infection (high IgG avidity, IgM negative) and 10 with indeterminate IgG avidity (IgM positive) which were tested for IgG avidity status with an in-house developed IgG avidity Western blot using the rGRA-7 recombinant antigen. All 20 sera from cases of probable acute infection showed bands which either faded out completely or reduced significantly in intensity after treatment with 8 M urea, whereas the band intensities of the 10 serum samples from chronic cases remained the same. Of the 10 sera with indeterminate IgG avidity status, after treatment with 8 M urea the band intensities with six sera remained the same, two sera had completely faded bands and another two sera had significantly reduced band intensities. Discrimination between acute and chronic toxoplasmosis was successfully performed by the in-house IgG avidity Western blot.

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii. Chronically-infected individuals with a compromised immune system are at risk for reactivation of the disease. In-vivo induced antigen technology (IVIAT) is a promising method for the identification of antigens expressed in-vivo. The aim of the present study was to apply IVIAT to identify antigens which are expressed in-vivo during T. gondii infection using sera from individuals with chronic toxoplasmosis. Forty serum samples were pooled, pre-adsorped against three different preparations of antigens, from each in-vitro grown T. gondii and Escherichia coli XLBlue MRF', and then used to screen a T. gondii cDNA expression library. Sequencing of DNA inserts from positive clones showed eight open reading frames with high homology to T. gondii genes. Expression analysis using quantitative real-time PCR showed that SAG1-related sequence 3 (SRS3) and two hypothetical genes were up-regulated in-vivo relative to their expression levels in-vitro. These three proteins also showed high sensitivity and specificity when tested with individual serum samples. Five other proteins namely M16 domain peptidase, microneme protein, elongation factor 1-alpha, pre-mRNA-splicing factor and small nuclear ribonucleoprotein F had lower RNA expression in-vivo as compared to in-vitro. SRS3 and the two hypothetical proteins warrant further investigation into their roles in the pathogenesis of toxoplasmosis., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

To study the efficacy of ethanolic extract of B. monosperma bark in cafeteria and atherogenic diet fed rats and monosodium glutamate (MSG) obese rats, different doses (200, 400 and 800 mg/kg) of ethanolic extract of B. monosperma bark showed dose dependent decrease in body weight, daily food intake, glucose, lipids, internal organs' weight and fat pad weight in cafeteria and atherogenic diet fed rats and monosodium glutamate obese rats. The results suggested that B. monosperma has significant anti-obese activity.

To evaluate the effect of an antitumor activity of Terminalia catappa on lipid lowering activity in transplanted fibrosarcoma in Wistar albino rats. Methylcholantherene-induced fibrosarcoma was transplanted in rats. After 30(th) day when tumor became palpable, started the treatment of ethanolic extract of Terminalia catappa by orally (250 and 500 mg/kg) for a period of 20 days. The blood sample was collected on 21(st) day, and the liver and the kidney were also removed for studying the lipid profile in serum and the tissues. The levels of total cholesterol, triglycerides and very low density lipoprotein (VLDL) were markedly elevated and high density lipoprotein (HDL) was markedly decreased in the serum of tumor bearing rats. Significant alterations were also observed in the lipid profile of liver and kidney. These changes were significantly reversed in Terminalia catappa (500 mg/kg) treated animals. The reversal of altered lipid levels to normal values in rats with experimentally induced tumor was showed antitumor activity by Terminalia catappa.

Objective: This study was undertaken to evaluate the neuroprotective activity of Wedelia calendulacea against cerebral ischemia/reperfusion induced oxidative stress in the rats., Materials and Methods: The global cerebral ischemia was induced in male albino Wistar rats by occluding the bilateral carotid arteries for 30 min followed by 1 h and 4 h reperfusion. At various times of reperfusion, the histopathological changes and the levels of malondialdehyde (MDA), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s-transferase (GST), and hydrogen peroxide (H(2)O(2)) activity and brain water content were measured., Results: The ischemic changes were preceded by increase in concentration of MDA, hydrogen peroxide and followed by decreased GPx, GR, and GST activity. Treatment with W. calendulacea significantly attenuated ischemia-induced oxidative stress. W. calendulacea administration markedly reversed and restored to near normal level in the groups pre-treated with methanolic extract (250 and 500 mg/kg, given orally in single and double dose/day for 10 days) in dose-dependent way. Similarly, W. calendulacea reversed the brain water content in the ischemia reperfusion animals. The neurodegenaration also conformed by the histopathological changes in the cerebral-ischemic animals., Conclusion: The findings from the present investigation reveal that W. calendulacea protects neurons from global cerebral-ischemic injury in rat by attenuating oxidative stress.

Toxoplasma gondii is an important human pathogen with a worldwide distribution. It is primarily of medical importance for pregnant women and immunocompromised patients. Primary infection of the former is often associated with fetal infection, which can lead to abortion or severe neonatal malformation. Immunocompromised patients are at risk of contracting the severe form of the disease that may be fatal. Thus, detection of T. gondii infection with high sensitivity and specificity is crucial in the management of the disease. Toxoplasmosis is generally diagnosed by demonstrating specific immunoglobulin M (IgM) and IgG antibodies to toxoplasma antigens in the patient's serum sample. Most of the commercially available tests use T. gondii native antigens and display wide variations in test accuracy. Recombinant antigens have great potential as diagnostic reagents for use in assays to detect toxoplasmosis. Thus in this review, we address recent advances in the use of Toxoplasma recombinant proteins for serodiagnosis of toxoplasmosis.

Present study revealed the importance of endosulfan in mediating stress responses in Sorghum bicolor L. Moench (variety JP-1-1). The seeds treated with different concentrations (0.2, 0.4 and 0.6%) of endosulfan showed a significant decrease in percent germination over control. As the concentration increased, the shoot length, root length and biomass decreased. The amount of chlorophyll-a and protein decreased gradually with the increase in endosulfan concentration, whereas phenol and proline contents increased from 1.08 to 1.57 mg g(-1) and 0.18 to 0.98 mg g(-1), respectively. Chlorophyll-b decreased in 0.2% (0.97 mg g(-1)) as compared to control and revealed a gradual increase in 0.4% (1.11 mg g(-1)) and 0.6% (1.13 mg g(-1)). Endosulfan treatment suppressed the catalase and protease activity, but significantly increased the level of peroxidase, polyphenol oxidase, SOD and amylase enzymes. Lowerdose (0.2%) of endosulfan stimulated the activity of amylases.