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Aim The effect of anacardic acid impregnation on catheter surfaces for the prevention of Staphylococcus aureus attachments and biofilm formations were evaluated. Methods and results Silicon catheter tubes were impregnated using different concentrations of anacardic acids (0·002-0·25%). Anacardic acids are antibacterial phenolic lipids from cashew nut (Anacardium occidentale) shell oil. Anacardic acid-impregnated silicon catheters revealed no significant haemolytic activity and were cytocompatible against fibroblast cell line (L929). Sustained release of anacardic acids was observed for 4 days. Anacardic acid-impregnated silicon catheters efficiently inhibited S. aureus colonization and the biofilm formation on its surface. The in vivo antibiofilm activity of anacardic acid-impregnated catheters was tested in an intraperitoneal catheter-associated medaka fish infection model. Significant reduction in S. aureus colonization on anacardic acid-impregnated catheter tubes was observed. Conclusions Our data suggest that anacardic acid-impregnated silicon catheters may help in preventing catheter-related staphylococcal infections. Significance and impact of the study This study opens new directions for designing antimicrobial phytochemical-coated surfaces with ideal antibiofilm properties and could be of great interest for biomedical research scientists.

Skin cancer represents one of the most common cancers worldwide. Current treatment involves conventional surgery and oral or intravenous administration of immunotherapeutic and chemotherapeutic drugs, which is associated with systemic side effects. To minimize the side effects, we developed a α-chitin polysaccharide-based hydrogel containing anticancer drug plumbagin (0.3%). Plumbagin loaded α-chitin hydrogel (PCHG) were characterized chemically and physically. The in vitro release of plumbagin from the PCHG showed a slow and sustained release of 33.8% in 6 days. In vitro porcine skin permeation assays demonstrated skin permeation of plumbagin from PCHG was 35.05 ± 0.73% after 48 h. The skin permeation of plumbagin from PCHG was further enhanced to 49.86 ± 9.32% when permeation enhancers 1% tween 80 and 1% polyethylene glycol was added into the PCHG. The in vitro anticancer activity of PCHG containing 1% tween 80 and 1% polyethylene glycol was further validated against melanoma A375 cell line.

The study was conducted to identify the antiproliferative property and the mode of action of (Z)-ethylidene-4,6-dimethoxycoumaran-3-one (EDC), a novel compound isolated from the plant leaves of Pogostemon quadrifolius (Benth.), against prostate cancer cell lines PC-3 and DU-145. EDC inhibited the proliferation of PC-3 and DU-145 cell lines at micro molar concentrations. EDC strongly inhibited the clonogenic propagation of prostate cancer cells. EDC arrests the prostate cancer cells at G2/M phase of the cell cycle and then eventually leads to apoptosis, which was confirmed by DNA fragmentation assay and poly (ADP-ribose) polymerase cleavage western blot analysis. At sub-lethal concentrations, EDC inhibited the migration of PC-3 by 87.1% and DU-145 by 68.0%. Thus, the present study revealed the in vitro cytotoxic and anti-metastatic property of EDC against PC-3 and DU-145 cancer cells.

Alkylation of hydroxyl groups of flavonoids is known to increase their bioavailability, metabolic stability and also impart new bioactivities. Though partially alkylated flavonoids and related compounds occupy substantial chemical space, there is scant information on their biological activities. They are comparatively less accessible, therefore development of their general syntheses are desirable. Chalcones play key role in the biosynthesis of array of flavonoids. Taking cues from nature, bioinspired, ecofriendly syntheses of polyhydroxy- and partially alkylated flavonoids have been developed. Compared to conventional protection groups, methoxymethylation was found to be more useful for the protection of hydroxyl groups. A library of flavones, flavonols, isoflavones and biflavones has been prepared. A brief account of our ongoing effort towards syntheses of small molecules is summarized here. Biological screening of the synthesized compounds led to recognition of several hitherto unreported inhibitors of biomarkers for MMP’s, NFkB, carbonic anhydrase etc.

Earlier studies from our laboratory have identified Anacardic acid (AA) as a potent inhibitor of gelatinases (MMP-2 and 9), which are over-expressed in a wide variety of cancers (Omanakuttan et al., 2012). Disruption of the finely tuned matrix metalloproteinase (MMP) activator/inhibitor balance plays a decisive role in determining the fate of the cell. The present study demonstrates for the first time, that in addition to regulating the expression as well as activity of gelatinases, AA also inhibits the expression of its endogenous activators like MMP-14 and Extracellular Matrix MetalloProteinase Inducer (EMMPRIN) and induces the expression of its endogenous inhibitor, REversion-inducing Cysteine-rich protein with Kazal motifs (RECK). In addition to modulating gelatinases, AA also inhibits the expression of various components of the Epidermal Growth Factor (EGF) pathway like EGF, Protein Kinase B (Akt) and Mitogen-activated protein kinases (MAPK). Furthermore, AA also activates the expression of Sprouty 2 (Spry2), a negative regulator of EGF pathway, and silencing Spry2 results in up-regulation of expression of gelatinases as well as MMP-14. The present study thus elucidates a novel mechanism of action of AA and provides a strong basis for utilizing this molecule as a template for cancer therapeutics.

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2' ,7' -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway.

Elevated levels of carbonic anhydrase II (CA II) have been shown to be associated with cardiac hypertrophy and heart failure. Although arjunolic acid (AA) has a diverse range of therapeutic applications including cardio-protection, there have been no reports on the effect of AA on CA II. The present study describes for the first time, the novel zinc independent inhibition of CA II by AA. The molecular docking studies of AA indicated that the hydroxyl group at C 2 of the A-ring, which hydrogen bonds with the catalytic site residues (His64, Asn62 and Asn67), along with the gem -dimethyl group at C 20 of the E-ring, greatly influences the inhibitory activity, independent of the catalytic zinc, unlike the inhibition observed with most CA II inhibitors. Among the triterpenoids tested viz. arjunolic acid, arjunic acid, asiatic acid, oleanolic acid and ursolic acid, AA was the most potent in inhibiting CA II in vitro with an IC 50 of 9 μM. It was interesting to note, that in spite of exhibiting very little differences in their structures, these triterpenoids exhibited vast differences in their inhibitory activities, with IC 50 values ranging from 9 μM to as high as 333 μM. Furthermore, AA also inhibited the cytosolic activity of CA in H9c2 cardiomyocytes, as reflected by the decrease in acidification of the intracellular pH (pH i ). The decreased acidification reduced the intracellular calcium levels, which further prevented the mitochondrial membrane depolarization. Thus, these studies provide a better understanding for establishing the novel molecular mechanism involved in CA II inhibition by the non-zinc binding inhibitor AA.

Radioprotective action of gossypetin (GTIN) against gamma (γ)-radiation-induced oxidative stress in liver was explored in the present article. Our main aim was to evaluate the protective efficacy of GTIN against radiation-induced alteration of liver in murine system. To evaluate the effect of GTIN, it was orally administered to mice at a dose of 30 mg/kg body weight for three consecutive days prior to γ-radiation at a dose of 5 Gy. Radioprotective efficacy of GTIN were evaluated at physiological, cellular, and molecular level using biochemical analysis, comet assay, flow cytometry, histopathology, immunofluorescence, and immunoblotting techniques. Ionizing radiation was responsible for augmentation of hepatic oxidative stress in terms of lipid peroxidation and depletion of endogenous antioxidant enzymes. Immunoblotting and immunofluorescence studies showed that irradiation enhanced the nuclear translocation of nuclear factor kappa B (NF-κB) level, which leads to hepatic inflammation. To investigate further, we found that radiation induced the activation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK)-mediated apoptotic pathway and deactivation of the NF-E2-related factor 2 (Nrf2)-mediated redox signaling pathway, whereas GTIN pretreatment ameliorated these radiation-mediated effects. This is the novel report where GTIN rationally validated the molecular mechanism in terms of the modulation of cellular signaling system’ instead of ‘ This is the novel report where GTIN is rationally validated in molecular terms to establish it as promising radioprotective agents. This might be fruitful especially for nuclear workers and defense personnel assuming the possibility of radiation exposure.

Eleven biflavones (7a-b and 9a-i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor. Molecular docking studies suggest that unlike most of the known inhibitors, 9h inhibits MMP-2 and MMP-9 through non-zinc binding interactions.

Failure of treatment for cancer in clinic by radio/chemotherapy is generally attributed to tumour resistance. Therefore, it is important to develop strategies to increase the cytotoxicity of tumour cells by radiation in combination with unique tumour selective cytotoxic agents. We evaluated the potential of ellagic acid (EA) as an enhancer of oxidative stress in cancer cells. HepG2 cells were treated with EA (10 µM) for 12 h prior to exposure of single 7.5 Gy dose of irradiation. Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation, up regulation of p53 protein expression, decreased survival markers level like p-Akt, p-NF-kB and p-STAT3 which were significantly higher after radiation treatment alone. We also found that combination treatment increased G2/M phase cell population, decreased IL-6, COX–2 and TNF-α expression and caused a loss in mitochondrial membrane potential with decreased level of angiogenesis marker MMP-9. Over expression of Bax and activation of caspase 3 indicated the apoptosis of the cells. The results provided a strong unique strategy to kill cancer cells HepG2, using less radiation dose along with effective pro-oxidant dose of EA.

The configuration about the C2 C8 double bond for the major isomer of the natural product ethylidene-4,6-dimethoxycoumaran-3-one isolated from the shrub Pogostemon quadrifolius (Benth.) was consistently determined to be Z by the examination of long-range NOE contacts (ηH,Hs), chemical shifts (δCs), and scalar coupling constants (3JH8,H9, 1JH8,C8, 3JH8,C3, and 2JH8,C2) in conjunction with DFT calculations. The Js was found to be very amenable to the structural analysis and disparate in terms of their magnitude, and in the case of 2JH8,C2, by the sign.

To evaluate the protective effect of gossypetin (GTIN) against gamma (γ)-radiation-mediated DNA damage.Increasing concentrations (10-150 μM) of GTIN were incubated with supercoiled DNA 1 h prior exposure to γ-radiation in the range of 5-Gy absorbed dose from Co(60) γ source. To establish the effective protective concentration of GTIN, supercoiled DNA was pre-incubated with 50 μM of GTIN for 1 h followed by exposure of 5, 10 and 20 Gy doses of γ-radiation. Moreover, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical, hydroxyl radical, nitric oxide (NO) scavenging, metal chelating activity and ferric reducing antioxidant power (FRAP) of GTIN were measured and compared with standards. The flowcytometric analysis and radiation-induced genomic DNA damage by comet assay were employed to estimate the level of intracellular reactive oxygen species (ROS) using isolated murine hepatocytes.GTIN was able to effectively scavenge different free radicals in in vitro situations. It could significantly prevent radiation induced supercoiled and genomic DNA damage with reduced comet parameters. It also acted as a potent scavenger of the radiation induced ROS.GTIN ameliorated radiation-induced oxidative stress and DNA damage by its free-radical scavenging activity.

Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1' pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC₅₀ of 11.11 μM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

It has been shown earlier that plumbagin, a naturally occurring naphthaquinone has specific anticancer activity in BRCA1 blocked ovarian cancer cells. Plumbagin can induce estrogen dependent cell signaling and apoptosis in BRCA1 blocked ovarian cancer cells. Being a reactive oxygen species (ROS) generator and apoptosis inducing agent, plumbagin has immense potential as a promising anticancer agent. In this study we analyzed whether there would be increased anticancer activity if the positions of the functional groups on plumbagin were altered and further to analyze the detailed molecular mechanism of action of the lead molecule. Methods like MTT assay, apoptosis analysis by flow cytometry, assessment of mitochondrial membrane potential-Δψm , suppression subtractive hybridization, microarray, molecular docking and estrogen receptor-DNA binding activity by electrophoresis mobility shift assay (EMSA) were adopted for assessing the anticancer activity. Consequently we found that, plumbagin was the most potent anticancer agent when compared to structurally related compounds. The anti-cancer activities were in the order plumbagin > 1,4-naphthaquinone > juglone > lawsone > menadione. Molecular docking studies showed that plumbagin could be well docked in the receptor ligand complex of TRAIL-DR5 complexes to activate the extrinsic pathway of apoptosis. Since the antiproliferative activity of plumbagin could be reduced by inhibiting ERα, we speculated that plumbagin interferes with the binding of ERα to ERE and we confirmed this by EMSA. This study clearly indicates that plumbagin can induce multiple pathways of apoptosis and cell cycle arrest in BRCA1 blocked cells compared to unblocked cells.

GLUT4, a 12 transmembrane protein, plays a major role in insulin mediated glucose transport in muscle and adipocytes. For glucose transport, the GLUT4 protein needs to be translocated to the plasma membrane from the intracellular pool and it is possible that certain compounds may be able to enhance this process. In the present work, we have shown that gallic acid can increase GLUT4 translocation and glucose uptake activity in an Akt-independent but wortmannin-sensitive manner. Further analysis suggested the role of atypical protein kinase Czeta/lambda in gallic acid mediated GLUT4 translocation and glucose uptake.

Insulin stimulated GLUT4 (glucose transporter 4) translocation and glucose uptake in muscles and adipocytes is important for the maintenance of blood glucose homeostasis in our body. In this paper, we report the identification of kaempferitrin (kaempferol 3,7-dirhamnoside), a glycosylated flavonoid, as a compound that inhibits insulin stimulated GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes. In the absence of insulin, we observed that addition of kaempferitrin did not affect GLUT4 translocation or glucose uptake. On the other hand, kaempferitrin acted as an inhibitor of insulin-stimulated GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes by inhibiting Akt activation. Molecular docking studies using a homology model of GLUT4 showed that kaempferitrin binds directly to GLUT4 at the glucose transportation channel, suggesting the possibility of a competition between kaempferitrin and glucose during the transport. Taken together, our data demonstrates that kaempferitrin inhibits GLUT4 mediated glucose uptake at least by two different mechanisms, one by interfering with the insulin signaling pathway and the other by a possible competition with glucose during the transport.

It has been reported that Breast Cancer Susceptibility gene-1 & 2 (BRCA1 & 2 are potential molecular targets for chemoprevention by isoflavone genistein (4' 5, 7-trihydroxy isoflavone), in breast and prostate cancer cells. It is also known that BRCA1 has inhibitory activity on estrogen receptor-alpha and genistein's action on cells is mainly through modulation of estrogen receptor activity. The action of genistein with respect to BRCA1 status in ovarian cancer cells has not been reported so far. Therefore in this study, we analyzed the action of genistein on BRCA1 antisense blocked (AS4) and unblocked (NEO) BG-1 ovarian cancer cells. We found that genistein induced comparable cytotoxic effect in both AS4 and NEO cells, but through different pathways. We found that genistein induces caspase 8 dependent apoptotic pathway in NEO cells. Genistein inhibits estrogen receptor-alpha and activates BARD1 in BRCA1 blocked cells and induces estrogen receptor-beta and FAS in presence of BRCA1. It can be concluded that even though there is no difference in the extent of cell death or apoptosis, the molecular mechanism of action of genistein in inducing apoptosis is different in BRCA1 blocked and unblocked cells. This could partially explain the beneficial effects of genistein in both wild type and mutated BRCA1 estrogen receptor positive tumors.

Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections.

There is an emerging evidence that plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone) may have potential as a chemotherapeutic agent. However, the growth inhibitory mechanisms of plumbagin have remained unexplored. The aim of the study was to determine whether plumbagin-induced cell death in human cervical cancer cell line, ME-180, exhibited biochemical characteristics of apoptosis and to check whether N-acetyl-l-cysteine (NAC), which is a free radical scavenger, can reverse the cytotoxic effects of plumbagin. It can be concluded from the results that plumbagin inhibits the growth of ME-180 cells in a concentration and time-dependent manner. The cytotoxic effect of plumbagin induced cell death is through the generation of reactive oxygen species (ROS) and subsequent induction of apoptosis as demonstrated by the present data. Treatment of cells with plumbagin caused loss of mitochondrial membrane potential (DeltaPsi(m)), and morphological changes characteristic of apoptosis, such as the translocation of phosphatidyl serine, nuclear condensation, and DNA fragmentation. Moreover, plumbagin-induced apoptosis involved release of mitochondrial cytochrome c and apoptosis inducing factor (AIF), thus activation of caspase-dependent and -independent pathways, as shown by the plumbagin-mediated activation of caspase-3 and -9. Our results also show that pretreatment of ME-180 cells with NAC blocks plumbagin-induced loss of DeltaPsi(m) and subsequent release of cytochrome c, AIF, and caspase-9 and -3 activation, thus inhibiting the apoptotic ability of plumbagin.

X-ray single crystal analysis of 20-hydroxyecdysone (20E, 2 ), an important insect moulting hormone, isolated from Sesuvium portulacastrum Linn. was found to exhibit a unique stereochemical configuration revealing it to be a different conformer ( polymorph ) possessing the aliphatic chain atoms in a trans configuration. Moreover, the analysis also revealed the presence of three molecules of water of crystallisation thereby restricting the freedom of the aliphatic side chain.

In vitro assessment showed that H. rhamnoides (HrLE) extract possessed free radical scavenging activities and can protect gamma (gamma) radiation induced supercoiled DNA damage. For in vivo study, Swiss albino mice were administered with HrLE (30 mg/kg body weight) for 15 consecutive days before exposing them to a single dose of 5 Gy of beta radiation. HrLE significantly prevented the radiation induced genomic DNA damage indicated as a significant reduction in the comet parameters. The lipid peroxidation, liver function enzymes, expression of phosphorylated NFkappaB (p65) and IkappaBalpha increased whereas the endogenous antioxidants diminished upon radiation exposure compared to control. Pretreatment of HrLE extract ameliorated these changes. Based on the present results it can be concluded that H. rhamnoides possess a potential preventive element in planned and accidental nuclear exposures.

Seventeen flavonoids with different substitutions were evaluated for inhibition of nuclear factor-κB (NF-κB) signaling in the invasive breast cancer cell line MDA-MB-231. They were screened using an engineered MDA-MB-231 cell line reporting NF-κB activation. The modulation of expression of two NF-κB regulated genes involved in tumorigenesis, matrix metalloproteinase-9 (MMP-9), and cyclooxygenase-2 (COX-2) were also analyzed in these cells. Among the compounds tested, all except gossypetin and quercetagetin inhibited the activation of NF-κB, and the expression of MMP-9 and COX-2 to different degree. Methylated flavone, chrysoeriol (luteolin-3'-methylether), was found to be the most potent inhibitor of MMP-9 and COX-2 expressions. The effect of chrysoeriol on cell proliferation, cell cycle, apoptosis and metastasis was analyzed by established methods. Chrysoeriol caused cell cycle arrest at G2/M and inhibited migration and invasion of MDA-MB-231 cells. The structure-activity relations amongst the flavonoids as NF-κB signaling inhibitors was studied. The study indicates differences between the actions of various flavonoids on NF-κB activation and on the biological activities of breast cancer cells. Flavones in general, were more active than the corresponding flavonols.

The chemosterilant activity of two naturally occurring napthaquinones, plumbagin from Plumbago sp. and juglone from Juglans regia has been evaluated using the red cotton bug Dysdercus koenigii. Their activity were compared with synthetic napthaquinones, menadione, two benzoquinones, 2,6-dimethyl and 2,3,6-trimethylbenzoquinone and a hydroquinone 2,6-dimethylhydroquinone. As far as the authors are aware, the present investigation is the first systematic attempt to investigate the effects of quinones on different aspects of reproduction, namely mating behaviour, fecundity and fertility. All the above types of quinones have revealed adverse effects on the reproduction of D. koenigii, which were topically treated as 1-day-old adults with different doses of the compounds depending on their 50% lethality (LD 50 ) values. Analysis of the data revealed a highly statistically significant reduction in the number of eggs, their hatching and further development up to the final instar stage. The sterility index increased with the increase in the dose of any of the above compounds and was highest when both sexes were treated. Among the natural products, juglone induced more sterilizing effects than plumbagin at 5-10 μg/insect. Menadione caused sterility at a very low dose such as 0.5 μg. Of the two benzoquinones, the dimethylbenzoquinone acted at a much lower dose.

Plumbagin, a naphthoquinone occurring in the plants belonging to Plumbago sp. is known to have insect growth disrupting activities. In the present study, a comparative evaluation of bioactivities of related naphthoquinones, juglone and menadione and benzoquinones, 2,6-dimethylbenzoquinone and 2,3,6-trimethylbenzoquinone along with 2,6-dimethylhydroquinone have been undertaken using Dysdercus koenigii. The LD50 values of the compounds showed wide variation. Although all the test compounds disrupted the normal growth at sublethal doses, 2,6-dimethylbenzo- quinone and menadione showed activity at low doses.

The efficacy of diallyl disulphide (DADS), a constituent of garlic oil, as a hypolipidaemic and antioxidant agent was evaluated in rats. In normolipidaemic rats DADS, at doses ranging from 10 to 50 mg kg−1, decreased plasma triglyceride without affecting cholesterolaemia and fast-or noradrenaline-induced lipolysis. DADS proved effective in reducing fructose-induced hypertriglyceridaemia and dietary hypercholesterolaemia in rats, in the latter model DADS significantly raised both the HDL cholesterol and the HDL/VLDL + LDL cholesterol ratio. DADS proved ineffective on triton induced hyperlipidaemia. To gain insight into the antioxidant effect of DADS, hepatic and cardiac antioxidant enzyme activity and glutathione content were studied in rats fed on a high diet and DADS. The antioxidant enzyme activity was significantly enhanced whereas glutathione content was markedly restored in rats fed on a high fat diet simultaneously with DADS. Thus, it appears that DADS exert antioxidant protection by activating the associated antioxidant enzymes.

An arabinogalactan of mean M r 2.2×10 6 has been isolated from the dried stems of Tinospora cordifolia and examined by methylation analysis, partial hydrolysis and carboxyl reduction. Purified polysaccharide showed polyclonal mitogenic activity against B-cells, their proliferation did not require macrophages.

This work deals with the batch studies on stripping of actinides extracted by a mixture octyl(phenyl)-N,N-diisobutyl-carbamoylmethylphosphine oxide (CMPO) and tri-n-butyl phosphate (TBP) in n-dodecane (Truex solvent) from simulated high level waste (HLW) solution. The stripping of americium and plutonium from acid-bearing CMPO-TBP mixture is carried out using a mixture of weak acid, weak base and complexing agent as strippant. A mixture of formic acid, hydrazine hydrate and citric acid appeared to be best suited for efficient stripping of americium and plutonium. With appropriate modifications in the concentration of individual constitutents, this strippant can be used for the recovery of actinides from loaded Truex solvent with any acid content.

Intramolecular 1,2-arene-alkene photocycloaddition of 2-alkenyl-4-chromanones gave complex multicyclic oxatetracyclotetradecanediones which on internal photo- and microwave induced thermal rearrangements provided a diverse array of compounds with [3.3.0]bicyclooctane carbon frame work. The stereo- and regiochemical aspects as well as desymmetrization of alkenyl chromanones due to intramolecular 1,2-arenealkene photocycloaddition have also been discussed.

Low valent titanium mediated cleavage of Npropargyl bonds offers a facile, mild, and high yielding method for the deprotection of amines under neutral conditions. The methodology could be used for the chemoselective removal of propargyl groups from amines in preference to the allyl/benzyl counterparts and can be performed chemoselectively in the presence of methoxy, methylenedioxy, and chloro functionalities.

Reductive cleavage of benzylidene acetals using low-valent titanium reagent results in the formation of aryl alkanes and stilbenes. Aliphatic acetals, however, remain unaffected. This cleavage offers an attractive, alternate stereoselective route to stilbenes in a modified McMurry reaction.

A highly reactive, low-valent titanium (LVT) reagent has been prepared by the addition of substoichiometric amounts of iodine to the LVT species generated by Rieke's method (TiCl3−Li−THF). While the conventional McMurry reaction requires high temperatures and prolonged reaction times for the generation of olefins, the present activated LVT reagent is able to effect the reductive coupling of aliphatic as well as aromatic carbonyls to the corresponding olefins at lower temperatures and much reduced reaction times. The protocol is also useful for the intramolecular coupling reactions leading to the one-step synthesis of heterocycles. The temperature-controlled McMurry reaction provides enhanced diastereoselectivity and features an excellent chemoselectivity. In addition to the McMurry reaction, other SET-induced carbon−heteroatom (O, N) bond cleavages can also be carried out with the activated reagent at a fast rate and at a low temperature in high yields.

A new 8.1′ type neolignan, (8R,1′S or 8S,1′R)-4-[2-(1,3-benzodioxolo-5-yl)-1-methylethyl]-2,5-dimethoxy-1-propenyl-2,5-cyclohexadienone, hookerinone B a diastereomer of hookerinone A, and a pair of 8.3′ type diastereomeric neolignans, lancifolin C and lancifolin D, were isolated from the alchoholic extracts of the medicinal plant Piper hookeri. The absolute configurations of these neolignans and of a third diastereomeric pair, dihydroisofutoquinol A and dihydroisofutoquinol B, were established by nuclear magnetic resonance spectroscopic methods. © 1998 John Wiley & Sons, Ltd.

The radiolytic degradation of the extractant mixture 0.2 M octylphenyl-N,N{prime}-diisobutylcarbamoylmethyl phosphine oxide (CMPO) + 1.2 M tributyl phosphate in n-dodecane [to be utilized for the partitioning of minor actinides from high level waste (HLW) solutions of PUREX origin] has been investigated in contact with 3 M HNO{sub 3} or synthetic pressurized heavy water reactors (PHWR)-HLW solution under dynamic conditions. The distribution ratios of Am, Zr, Fe and Ru with the irradiated extractant mixture at varying doses have been determined under various aqueous phase conditions and correlated with the formation of degradation products. Various cycles of loading the extractant mixture with Am from PHWR-HLW, irradiating at a fixed gamma dose, and then primary and secondary clean-up of the solvent has been carried out to illustrate its reusability during partitioning of minor actinides from actual HLW solutions. The degradation products of CMPO have been identified by employing GC and GC-MS techniques.

The stereochemistry of the tertiary hydroxyl group in diterpene furan glycosides viz. cordifolisides D (1) and cordifoliside E (2) has been assigned on the basis of pyridine solvent induced shifts (PIS) in the 1H and 13C NMR spectra. The methyl and the methylene groups occupying positions vicinal, 1,3-diaxial and geminal to the tertiary hydroxyl group were deshielded to different extent depending on the dihedral angle. The stereochemical assignments are well supported by 13C-γ shifts and 2D Overhauser spectroscopy.

A novel transformation of 7-hydroxy-2-methyl-2-(4-methyl-3-pentenyl)-4-chromanone ( 1 ) to intramolecular 1,3-arene-alkene photocycloadduct, (1 S ,2 R ,5 S ,7 S ,10 S ,13 R )6,6,10-trimethyl-14-oxapentacyclo[8.3.1.0 1,7 .0 2,13 0 5,13 ] tetradecane-3,12-dione ( 3 ) via secondary photorearrangement of 1,2-arene-alkene photocycloadduct ( 2 ) has been described.

The influence of a protected alcohol group adjacent to the ene or enophile component on diastereoselectivity in both thermal and Lewis acid-catalyzed 5-(3,4) ene reactions of a series of 1,6-dienes 1−7 has been studied. The results indicate that its effect can be considerable, and in one example, with a gem-dimethyl group on the connecting chain and a large silyl protecting group on the hydroxyl, the diastereocontrol was almost perfect, with three stereogenic centers and one double bond geometry set up in one step, e.g., 4 → 10. This new finding was exploited in a synthesis of epijasmonoid natural products, (±)-methyl cucurbate (19) and (±)-methyl epijasmonate (18) starting from aldehyde 24, where the key step was a highly diastereocontrolled 5-(3,4) ene cyclization 23 → 22.

Investigations on molecular interactions of C60 with a variety of solvents show that its solubility is largely controlled by efficient charge transfer interactions between electron deficient C60, with suitable n-and π-donors. Organic species having a lone pair of electron on heteroatoms (n-donors) and/or π-electron cloud (π-donors) which are capable of forming charge transfer complexes with C60, are better solvents. Solvent-C60 interaction studies thus help in the rational design of solvents and has led to the discovery of several new classes of solvents such as brominated aliphatic hydrocarbons, nitrogen heterocycles, alkylated aromatics, aryl-alkyl ethers and bromoaryl-alkyl ethers. A detailed NMR study gave insight into the nature of molecular interactions.

The partitioning and recovery of237Np from three types of simulated high level waste solutions originating from PUREX processing of spent nuclear fuels such as sulfate bearing high level waste (SB-HLW), HLW from a pressurised heavy water reactor (PHWR-HLW) and from a fast breeder reactor (FBR-HLW) have been carried out using a mixture of 0.2M CMPO and 1.2M TBP in dodecane. Quantitative extraction of neptunium was possible by either oxidizing it to the hexavalent state keeping K2Cr2O7 at 0.01M concentration or by reducing it to tetravalent state keeping Fe2+ at 0.02M concentration. Stripping of neptunium was carried out using different reagents, such as dilute nitric acid, oxalic acid and sodium carbonate. Almost quantitative recovery of neptunium has been achieved during these studies.

The reduction of aryl aldehydes and ketones in neutral medium, to the corresponding hydrocarbons via carbon-nitrogen bond cleavage of the intermediate N-(arylmethyl)anilines with low-valent titanium reagents is described. It provides a mild, convenient and selective pathway for deoxygenation of carbonyls without the production of any side product.

Enantiomers of pyridyl-1-ethanols have been prepared via microbial reduction of pyridyl-1-ethanones and hydrolysis of (±)-pyridyl-1-ethyl acetates using Rhizopus arrhizus.

Influence of various external ligands/auxiliaries on the reductive carbonyl coupling reactions mediated by low-valent titanium (LVT) reagents (McMurry coupling) has been explored. The LVT species generated from Tyrlik's TiCl3−Mg−THF system has been selected for the reactivity-tuning trials. Our studies show that incorporation of about 10 equiv of pyridine (a π-acceptor ligand) with respect to TiCl3 to the THF solvated LVT reagent could arrest the reductive dimerization of acetophenone at the intermediate pinacol stage. Modulation of the LVT-species by covalently-binding monohydroxy, 1,2- and 1,3-dihydroxy auxiliaries also resisted deoxygenation completely to give the pinacols in higher yields and better diastereoselectivity, as compared to pyridine-modified LVT system. Amongst these modified reagents, the LVT−catechol (1:1) system was found to be the most efficient combination for total pinacolization of aromatic carbonyl compounds, even under refluxing conditions. The actual titanium reagent responsible ...

The fungus Rhizopus arrhizus has been used for the reduction of acetophenone and its o -, m - and p -methoxy derivatives 1a–d to the corresponding ( S )-(−)-alcohols. Their racemic acetates were also hydrolyzed to ( R )-(+)-alcohols. The analysis of products revealed that maximum enantioselectivity (78–88 %ee) could be obtained using m -methoxy acetophenone as substrate.

Two new norditerpene furan glycosides (cordifoliside D and cordifoliside E) were isolated, as their tetraacetates, from the polar butanol extract of Tinospora cordifolia stems. The structural elucidations and relative configurations are based on high-resolution 1D and 2D NMR spectroscopy.

Bench-Scale studies on the partitioning and recovery of minoractinides from the actual and synthetic sulphate-bearing high level waste (SBHLW) solutions have been carried out by giving two contacts with 30% TBP to deplete uranium content followed by four contacts with 0.2M CMPO+1.2M TBP in dodecane. The acidity of the SBHLW solutions was about 0.3M. In the case of actual SBHLW, the final raffinate contained about 0.4% α-activity originally present in the HLW, whereas with synthetic SBHLW the α-activity was reduced to the background level.144Ce is extracted almost quantitative in the CMPO phase,106Ru about 12% and137Cs is practically not extracted at all. The extraction chromatographic column studies with synthetic SBHLW (aftertwo TBP contacts) has shown that large volume of waste solutions could be passed through the column without break-through of actinide metal ions. Using 0.04M HNO3>99% Am(III) and rare earths could be eluted/stripped. Similarly >99% Pu(IV) and U(VI) could be eluted.stripped using 0.01M oxalic acid and 0.25M sodium carbonate, respectively. In the presence of 0.16M SO 4 2− (in the SBHLW) the complex ions AmSO 4 + , UO2SO4, PuSO 4 2+ and Pu(SO4)2 were formed in the aqueous phase but the species extracted into the organic phase (CMPO+TBP) were only the nitrato complexes Am(NO3)3·3CMPO, UO2(NO3)2·2CMPO and Pu(NO3)4·2CMPO. A scheme for the recovery of minor actinides from SBHLW solution with two contacts of 30% TBP followed by either solvent extraction or extraction chromatographic techniques has been proposed.

A novel low-valent titanium (LVT) mediated cleavage of N-allyl/benzyl amines is reported. Regio- and chemo-selective cleavages were also observed.

An extraction chromatographic technique using octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) adsorbed on chromosorb-102 (CAC) has been tested as an alternative to the TRUEXsolven...

A novel low-valent titanium (LVT) induced one-pot synthesis of phenanthrenes (25–38% yield) from ortho-alkoxy aromatic aldehydes/ketones was reported by us earlier. Activity of LVT complex could be modulated rationally by using catalytic amount of pyridine. Use of this LVT-pyridine reagent system improved the yields of phenanthrenes (3) by two folds.

Addition of catalytic amounts of fullerenes as coordinating ligand to the low valent titanium reagent resulted in the remarkable increase in the yields of phenanthrenes (3) from orthomethoxy aryl aldehydes/ketones (1) (SCHEME I) via intramolecular C-C coupling. This is the first report on the use of fullerenes as a ligand in transition metal mediated organic synthesis.