7,8-dihydroxyflavone-functionalized gold nanoparticles target the arginase enzyme of Leishmania donovani.

Aim: To analyze the efficacy and possible mechanism of action of 7,8-dihydroxyflavone (DHF) and DHF synthesized gold nanoparticles (GNPs) against the parasite Leishmania donovani. Methods: GNPs were synthesized using DHF and characterized by dynamic light scattering, ζ potential, Fourier transform infrared spectroscopy, transmission electron microscopy and x-ray diffraction. The efficacy of DHF and DHF-GNP were tested against sensitive and drug-resistant parasites. GNP uptake was measured on macrophages by atomic absorption spectroscopy. Results: DHF and DHF-GNP (∼35 nm) were equally effective against sensitive and drug-resistant strains and inhibited the arginase activity of parasites. Increased IFN-γ and reduced IL-12 cytokine response showed a Th1/Th2-mediated cell death in macrophages. Conclusion: The low cytotoxicity and high biological activity of DHF-GNP may be useful for chemotherapy of leishmaniasis.

Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice.

BACKGROUND & OBJECTIVES: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. METHODS: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 µg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. RESULTS: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. INTERPRETATION & CONCLUSIONS: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action.

Ebselen abrogates TNFalpha induced pro-inflammatory response in glioblastoma.

We investigated the pro-inflammatory response mediated by TNFalpha in glioblastoma and whether treatment with organoselenium Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]one) can affect TNFalpha induced inflammatory response. Exposure to TNFalpha increased the expression of pro-inflammatory mediator interleukin IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and cyclooxygenase (COX-2). Treatment with Ebselen abrogated TNFalpha induced increase in pro-inflammatory mediators. Ebselen not only abrogated TNFalpha induced enhanced invasiveness of glioma cells by down-regulating matrix metallo proteinase (MMP-9) and urokinase plasminogen (uPa) activity, but also inhibited glioma cell migration. Treatment with Ebselen also down-regulated the enhanced ROS production of TNFalpha treated glioma cells. In addition, Ebselen induced DNA damage repair signaling response in glioma cells both in the presence and absence of TNFalpha. These studies indicate that together with its known ability to sensitize glioma cell to TNFalpha induced apoptosis, Ebselen can overcome TNFalpha induced pro-inflammatory mediators to prevent a build up of a deleterious pro-inflammatory tumor microenvironment.

Role of hydrogen bonding on the spectroscopic properties of thiazolidinedione derivatives in homogeneous solvents.

In this work, three newly synthesized derivatives of thiazolidinediones, with potential for application as drugs in pharmaceutical industry and free radical scavenging activity, have been taken up to investigate their behaviour in different homogeneous solvents. The purpose of this work is to study the solvation characteristics in ground and excited states of the derivatives by monitoring the absorbance and fluorescence band maxima. The steady state and time resolved fluorescence studies in protic and aprotic solvents have been rationalized on the basis of solute-solvent interaction and substituent effect on these photophysical processes have been analyzed. Substituents at different positions of the aryl moiety affect the hydrogen bond formation ability of the probes.

Protective effect of diphenylmethyl selenocyanate against CCl4-induced hepatic injury.

Organoselenocyanates represent an important class of chemopreventive agent, which possess antioxidative, antimutagenic as well as cancer chemopreventive properties. The present study is an attempt to evaluate the protective effect of diphenylmethyl selenocyanate -- a synthetic organoselenocyanate against carbon tetrachloride (CCl(4))-induced hepatic damage in Swiss albino mice in vivo. Mice were pretreated with the Se-compound orally in a duration dependent manner (7 and 15 days) to observe its protective action against an acute toxic dose (24 h) of CCl(4) (single injection at a dose of 20 microl and 50 microl kg(-1) b.w.) that induced hepatic necrosis and caused DNA damage (strand breaks) in the hepatocytes. This study revealed that pretreatment with the Se-compound reduced the extent of massive hepatic necrosis in a duration dependent manner, but it had no modulatory effect on hepatocellular apoptosis caused by acute toxic doses of CCl(4). It was also found that the Se-compound could significantly (P < 0.01) prevent the CCl(4)-induced elevation of DNA damage in hepatocytes measured by comet assay in a duration dependent manner. So these findings will further strengthen the view that organoselenocyanate is an effective chemopreventive agent against acute hepatic damage, caused by halogenated alkanes such as CCl(4).

Synthesis of O-prenylated and O-geranylated derivatives of 5-benzylidene2,4-thiazolidinediones and evaluation of their free radical scavenging activity as well as effect on some phase II antioxidant/detoxifying enzymes.

A series of 5-arylidene-2,4-thiazolidinediones and its geranyloxy or prenyloxy derivative were synthesized and studied for their radical scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Their comparable scavenging activities were expressed as IC50 value. Compounds 2c, 2d, 4d, and 6a showed appreciable radical scavenging activities. The vanillin based thiazolidinedione compound 2c displayed highest activity comparable to that of alpha-tocopherol. But in vivo, compound 6a showed better results in inducing phase II detoxifying/antioxidative enzyme.

Spectroscopic studies of 2-(2-bromo-ethyl)-6-nitro-benzo[de]isoquinolene-1,3-dione in water/alkanol mixed solvents and nonionic micelle of Igepal CO series.

Spectroscopic studies of newly synthesized bioactive compound 2-(2-bromo-ethyl)-6-nitro-benzo[de]isoquinolene-1,3-dione (BNBIO) have been carried out in polar aprotic solvent, viz. acetonitrile, tetrahydrofuran, 1,4-dioxan, ethylene glycol, dimethyl formamide, and polar protic solvent, viz. methanol, ethanol, propanol, water. Variation in absorbance of BNBIO in water-methanol, water-ethanol and water-propanol mixtures at their different compositions have been observed. Absorption behaviour of the dye has been studied in poly(oxyethylene) nonylphenol surfactants Igepal CO 630, Igepal CO 720 and Igepal CO 890 containing same hydrophobic tail and different numbers of poly(oxyethylene) groups. Experimental results of the BNBIO nonionic micelles have been explained in terms of 1:1 electron donor-acceptor (EDA) complexation and the complexation equilibrium becomes suppressed with increasing number of poly(oxyethylene) residue on the Igepal surfactant. Variation in binding constant of dye-micelle complexation has been rationalized considering a competitive equilibrium process between the BNBIO-water interactions.

2-(2-Selenocyanic acid ethyl ester)-1H-benz[de] isoquinoline-1,3-(2H)-dione, synthesis photophysics and interaction with bovine serum albumin: a spectroscopic approach.

The compound 2-(2-selenocyanic acid ethyl ester)-1H-benz[de] isoquinoline-1,3-(2H)-dione (SEBID), a ubiquitous, bioactive naphthalimide derivative is expected to possess an anticancer, anti-tumor and other important therapeutic activities of significant potency with low systematic toxicity. In this paper, the synthesis of the compound, photophysics of the newly prepared naphthalimide derivative and its interaction with model transport protein Bovine serum albumin (BSA) have been reported using the absorption and steady state fluorescence spectroscopic techniques exploiting the intrinsic fluorescence emission properties of BSA as a probe. Interaction of this organoselenium compound in different dioxane-water mixtures with increase in the polarity of the medium has been studied spectroscopically. Interaction of SEBID with BSA leads to a dramatic decrease in the fluorescence intensity of BSA, which suggests the binding of SEBID with the tryptophan residue of BSA. Furthermore, different thermodynamic parameters for SEBID-BSA interaction have been calculated. Rationalization of the data has been attempted, particularly in relation to prospective applications in the biomedical research.

Synthesis and evaluation of antioxidative properties of a series of organoselenium compounds.

A series of organoselenocyanate compounds 4a-d were synthesized utilizing 1,8-naphthalic anhydride as the building unit. These compounds were evaluated for their antioxidative activities against DMBA-PMA-induced oxidative stress in a two-stage mouse skin carcinogenic model. Compound 4d was found to have the maximum antioxidative property in comparison with the other compounds. Also, the pretreatment group showed better results than the concomitant treatment groups.