Search

A lysosomal targeting naphthalimide-benzimidazole based probe has been designed, synthesized and evaluated for detecting lysosomal pH changes inside living cells. The probe displays highly selective and sensitive response towards pH changes in aqueous medium. The sensing mechanism involves intramolecular charge transfer from benzimidazole moiety to naphthalimide core. The portable kits were also designed to demonstrate real time application of the probe. Probe 2 was successfully applied to cells and nematodes and all the findings emphasized that it can easily detect the lysosomal pH changes in living cells. To emphasize the ability of probe 2 for determining the lysosomal alkalinisation, a cell based model study was performed using lysomotropic regent chloroquine, results of which demonstrated that probe 2 has the potential for monitoring dynamic pH changes in living systems.

The Fsup-/supion and viscosity both affect the physiological state of mitochondria and to the best of our knowledge no fluorescent probe is reported for the dual detection of mitochondrial viscosity and Fsup-/supion through different signals. DMAS-Si is weakly red fluorescent due to free intramolecular rotation between dimethylaminophenyl and pyridinium moieties and PET from silyloxy to the pyridinium moiety. In viscous medium (glycerol 90 %), the rotation is restricted and 18-fold increase in red-fluorescence (λsubem/sub637 nm) is observed. On reaction with Fsup-/supion, the desilylations followed by release of quinone-methide from DMAS-Si gives intense green fluorescence (λsubem/sub515 nm) due to formation of DMAS. DMAS-Si can detect as low as 50 nM Fsup-/sup. DMAS-Si shows good permeability to HeLa cells and preferably targets mitochondria. It has been used for imaging of increased viscosity in mitochondria of HeLa cells in the presence of nystatin through red fluorescence and exogenous Fsup-/supion by appearance of green fluorescence.

The detection of Cu2+ and ClO− is important in many fields such as medical diagnostic and waste water treatment. The chromo-fluorescent probes have an edge over the traditional methods however few probes applied for dual detection of Cu2+ and ClO− ions. Herein, A new dual function ratiometric ‘turn-on’ chromo-fluorescent probe based on perylene tetra-(octyloxycarbonyl) dye containing N,N’-dimethylethylenediamine (PTAC-1) was synthesized and investigated for applications. It showed selective response for Cu2+ ions in CH3CN-H2O (7:3, v/v) with ratiometric absorption (A460nm/A521nm) and emission (F495nm/F660nm) changes with detection limits 94 nM and 2.5 nM, respectively. Dramatic colour changes in dye upon addition of 100 nM Cu2+ ions provide an excellent but rare example of visible naked eye detection. The inactive PTAC-1 + Cu+ mixture was used for the detection of ClO− via in-situ oxidation of Cu+ to Cu2+ with high selectivity. The detection limits were 374 nM and 6.09 nM. PTAC-1 was successfully used for bioimaging of Cu2+ and ClO− ions in MG-63 cells, developing solid- and solution-based diagnostic test kits for Cu2+ ions; for quantification of Cu2+ and ClO− ions in real samples including water, soil, urine and disinfectant. The complexation mechanism with Cu2+ or ClO− was confirmed by Job’s plot, SPECFIT, NMR, DLS titrations, IR, TGA and AFM studies.

Cancer is a leading cause of disease burden throughout the world. Many cancers develop as a result of exposure to both lifestyle and environmental factors that are potentially modifiable. In the last few years, much of the scientific attention has drawn to the discovery of new and effective chemopreventive agents from natural sources. A multitude of phytoconstituents have been explored for their potential to prevent the occurrence of carcinogenesis both in vitro and in vivo by means of diverse cellular and molecular approaches. Key focus of this review is to highlight some significant and new information about different molecular aspects of chemopreventive ability of plant based phytochemicals in terms of their inhibitory potential on cancer growth. In addition, information regarding certain limiting factors such as whole animal physiology, tumour microenvironment and bioavailability of active components of phytoconstituents used in pre/clinical trials are further explored. This review would further assist the scientific community involved in designing efficacious chemopreventive approaches using these phytochemicals in treating cancer.

Designing of chemodosimetric probe for detection of H2S and Hg2+ at nanomolar level is highly important and challenging because of their toxicity to living organisms and the environment. Herein, we report unique chemodosimeteric design approach, where perylene diimide core is threaded by dual-react able sites for selective detection of H2S and Hg2+ in water. PDI 3 retained its chromophoric properties in solution, solid state and could be used to develop solution/solid state-based diagnostic kits for on-site detection of certain concentrations of H2S (0.034–0.5 ppm). PDI 3 showed ultra-sensitivity for H2S (UV–vis = 4.6 nM and Fluorescence = 19.5 nM) and Hg2+ (UV–vis = 60 nM and Fluorescence = 33 nM) in solution and 140 pg/cm2 and 19.9 pg/cm2 respectively using TLC strip (solid state). Kinetic profiles of PDI 3 showed the completion of the reaction within 14 min with pseudo-first order rate constant (k = 5.13 × 10−1/min). PDI 3 has good permeability, low cytotoxicity and was successfully applied for H2S and Hg2+ bio-imaging in MG-63 cells and for determination of H2S in human serum and urine samples.

Novel formulation using a dual approach of nanoparticles-loaded in situ hydrogel to overcome the severe toxicity associated with conventional intravenous formulations like high systemic toxicity, frequent dosing, burst release, non-specific distribution, and poor therapeutic efficacy was developed. Carboplatin-loaded ethyl cellulose nanoparticles were prepared using double emulsion solvent evaporation method and characterized for size (213.8 ± 2.5 nm), shape and encapsulation efficiency (52.24 ± 3.1%). Optimized nanoparticle incorporated within in situ hydrogel base sustained the drug release for 7 days (94.53 ± 0.91%) whereas, pure drug and commercial counterpart showed burst release within 2 h. Further, rheology studies confirmed the formation of hydrogel at 37 ± 0.13 °C. Furthermore, ex vivo (hemolytic and cytotoxicity) and in vivo toxicity studies demonstrated better safety and tolerance of developed hydrogel in comparison to commercial. Pharmacokinetic and biodistribution studies showed the localized and sustained release behaviour of optimized formulation (MRT- 20.3 ± 1.01 h) in comparison to its commercial (MRT- 7.8 ± 0.3 h). In addition, good anti-tumor activity of hydrogel was also observed as evaluated using ehrlich ascitic carcinoma mice model. Thus, developed in situ hydrogel could be a safe and efficient delivery system for sustained and localized delivery of carboplatin and improved patient compliance.

The present study is intended to investigate the influence of SrO doping in SiO2–CaO–MgO–P2O5 (varying SrO as 0, 1, 3 & 5 mol %) sol-gel derived bioceramics. The impact of strontium doping on structural and biological properties is assessed using X-ray diffraction (XRD) analysis, Fourier transform infrared (FTIR) spectra, degradability in simulated body fluid (SBF), Brunauer-Emmett- Teller (BET), Barret-Joyner-Halenda (BJH) and anti-oxidant activity against hydrogen peroxide (H2O2) induced oxidative stress using cell culture studies. Field emission scanning electron microscopy with energy dispersive X-ray (FESEMM-EDX) technique is used for morphological studies. The in vitro tests demonstrate that incorporation of strontium does not hinder the precipitation of the hydroxyapatite. The Zeta potential studies reveal that samples possessed negative surface charge, which might promote the binding and augmentation of osteoblasts. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell proliferation assay conducted on human osteosarcoma MG-63 cell line indicate significant cell survival. With regard to the antioxidant properties, samples with the highest concentration of strontium exhibits maximum protection against hydrogen-induced oxidative stress in cell culture. Thus, our studies suggest that SrO doped bioceremics demonstrate excellent physical and biological properties and strongly present their candidature as successful implant materials.

The present study focuses on the study of influence of CeO2 substitution on the structural, in vitro bioactivity, degradation, osteoblasts proliferation, oxidative stress and cell apoptosis induction in the sol-gel derived 34SiO2·8P2O5·17MgO.xCeO2.(41-x)CaO (x = 0, 0.5, 2.5 and 5 mol%) bioceramics. Zeta potential measurements were undertaken and it has shown two sign reversals with time when samples were immersed in simulated body fluid. This is mainly attributed to the adsorption of the cations from the samples and the second reversal is speculated to be due to the precipitation of the PO43− from the body like fluids. Results revealed that samples containing high amounts of cerium decrease bioactivity by forming the cerium phosphate instead of hydroxyapatite on their surfaces. In spite of the decrease in growth rate of hydroxyapatite layer formation, it is observed that maximum protection towards the oxidative stress induced by hydrogen peroxide and apoptosis is favored for higher amounts of cerium-containing samples exhibiting maximum cell viability. Our results indicate that the “sol gel” synthesis technique promotes hydroxyapatite growth rate over conventional “melt quenching” route.

Design of ratiometric probes which can differentiate bioactive sulphur species (H2S, Cys and GSH) are in demand. In this work, perylenediimide–7-nitro-2,1,3-benzoxadiazole based near-IR chromofluorescent probe (NBD-PDI) was designed for discriminative detection of H2S and Cysteine. The chemodosimetric reaction of NBD-PDI with H2S induces cleavage of the NBD moiety via thiolysis and thereby affords PDI-OH (λmax 680 nm) and NBD-SH (λmax 550 nm) with diminution of emission intensity at 537 nm. Meanwhile after the reaction of NBD-PDI with cysteine, only absorbance at 680 nm observed while emission at 660 nm decreased and 537 nm increased. The intensities of NBD-PDI showed linearity with increase of H2S and Cys concentrations with detection limits of 3.29 μM and 13.5 μM (UV–vis); 1.3 μM and 3 μM (fluorescence), respectively. Moreover, applicability of NBD-PDI for the fluorescence imaging of H2S and cysteine in MG-63 cells was investigated. The unique differential response of NBD-PDI towards H2S and Cysteine allowed fabrication of IMP, INH, OR, NOR and TRANSFER logic gates. NBD-PDI coated TLC strips can be used for visualization of H2S/Cysteine and for writing alphabets using H2S/Cysteine as ink. The mechanism of H2S interaction using 1H NMR titration, DFT and CV studies are also discussed.

We report design and synthesis of heterogeneously bay functionalized perylenedimide PN-PDI, endowed with two differentialy reacting functional groups –NO2 and propargyloxy, as dual analyte chemodosimeter for differential and instantaneous colorimetric (NIR) and fluorescence responses towards H2S and Pd0 with vivid color changes. The respective colorimetric and fluorescent detection limits for H2S (1.21 nM and 6.6 nM) and Pd0 (3.05 nM and 3.3 nM) are based on S/N = 3. Furthermore, the practical utility of PN-PDI for the detection of H2S and Pd0 has been demonstrated in blood serum, urine and live A549 cells. PN-PDI based test strips can be used to detect H2S 2.8 pg/cm2 and Pd0 11.5 pg/cm2 by the naked eye. The results of UV–vis, fluorescence spectroscopic and 1H NMR titration studies confirm that mechanism of H2S sensing is through both reduction of –NO2 group to –NH2 and thiolysis reactions, whereas mechanism of Pd0 sensing is through depropargylation reaction of propargyloxy group in PN-PDI. The multiple outputs have been further utilized to construct NOR and INH logic functions.

Objective: The use of natural phytoconstituents for food and as nutritional supplements is an easiest way to be healthier. Anthraquinone pigments have been traditionally used for various purposes viz. food colorants, textile staining, color paints and medicines. Rubia cordifolia L. is a perennial, herbaceous climbing plant belonging to family Rubiaceae. This plant contain substantial amounts of anthraquinones, especially in the roots. The present study deals with the bioactivity evaluation of phytoconstituents viz. alizarin and purpurin from Rubia cordifolia. Methods: The DNA protective and antioxidant potential of alizarin and purpurin was evaluated using different in vitro assays viz. DNA protection assay, ABTS assay, DPPH assay, Ferric ion reduction potential and Phosphomolybdenum assay. Results: Alizarin and purpurin exhibited good free radical scavenging activity in various assays. In DNA protection assay, alizarin showed more DNA protection against hydroxyl radicals generated by Fenton ’s reagent in comparison to purpurin. Conclusions: Being potent antioxidants, these natural coloring compounds can be boon to the food industry as nutraceuticals. Further, these phytochemicals can be explored for their anticancer activity and may serve as potent cancer chemopreventive molecules.

Rubia cordifolia L. (Rubiaceae) is an important medicinal plant used in the Ayurvedic medicinal system. Its use as a traditional therapeutic has been related to the treatment of skin disorders and cancer. Besides its medicinal value, anthraquinones from this plant are used as natural food colourants and as natural hair dyes. Dyes derived from natural sources have emerged as important alternatives to synthetic dyes. Alizarin (1,2-dihydroxyanthraquinone) was isolated and characterized from R. cordifolia L. and evaluated for its antigenotoxic potential against a battery of mutagens viz. 4-nitro-o-phenylenediamine (NPD) and 2-aminofluorene (2-AF) in Ames assay using TA98 tester strain of Salmonella typhimurium; hydrogen peroxide (H(2)O(2)) and 4-nitroquinoline-1-oxide (4NQO) in SOS chromotest using PQ37 strain of Escherichia coli and in Comet assay using human blood lymphocytes. Our results showed that alizarin possessed significant modulatory role against the genotoxicity of mutagens.

By combining the structural features of acridone based anti-cancer drugs (like amsacrine) and MDR modulator propafenone, acridones with hydroxyl amine chain at N-10 have been designed and synthesized. These molecules exhibit appreciable interactions with p-gp and Mg2+ indicating their suitability to modulate p-gp mediated multi drug resistance.

5-Hydroxymethyl-/carboxyl-2,3-diaryl-tetrahydro-furan-3-ols have been investigated for their COX-1 and COX-2 inhibitory activities. Compounds 17, 18 and 20 have been identified as showing appreciable COX-2 inhibition and selectivity. The group present at C-5 of tetrahydrofuran and the substituents at the two phenyl rings, through their interactions with active site amino acid residues, significantly affect the activities of these molecules. The quantitative structure-activity relationship studies indicate the role of logP, TPSA, molecular connectivity and valence connectivity towards the activities of these molecules.

Indoles carrying a cyclic ester (gamma-butyrolactone) at C-3 position have been synthesized by the allylation of 3-indoleglyoxylate followed by iodocyclisation and the nucleophilic replacement of the iodo-group. Screening of these molecules for COX-2 inhibition and anti-cancer activities has identified compounds 10 and 11 as highly potent and selective for COX-2 as well as showing remarkable anti-cancer activities (better than that of indomethacin).

The genotoxicity of wastewater samples from sewage, and industrial effluent from the Amritsar, India, area were investigated using the Allium micronucleus and anaphase aberration assays. Raw sewage samples and acetone extracts of the dehydrated sewage were use for treatment of the Allium roots. Industrial effluents were collected and stored in the form of sludge (semi-dried matter). The acetone extracts of the sludge samples were also used for treatment of the Allium roots. From the Allium root micronuclei tests on the sewage extracts, no significant increase in the number of micronuclei was found in comparison with negative controls. All the other extracts from industrial effluent showed positive responses both in the micronucleus and anaphase aberration assays.

A tannin fraction (TC-E) from the dried fruit pulp of Terminalia chebula was obtained by successfully extracting with 95% ethyl alcohol and ethyl acetate. TC-E was subjected to silica gel chromatography which yielded four fractions, viz., TC-EI, TC-EII, TC-EIII and TC-EIV. Thin layer chromatography (TLC) and 13C-NMR revealed that TC-EI was gallic acid (GA) derivative while the other fractions were tannin in nature. TC-E and its fractions were evaluated for their antimutagenic potential against two direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and 4-nitroquinoline-N-oxide (4NQNO), and S9-dependent mutagen, 2-aminofluorene (2AF) in TA98 and TA100 strains of Salmonella typhimurium. The study revealed that the extract (TC-E) and its fractions were highly significant against S9-dependent mutagen, 2AF. The effect was found to be more or less corresponding with the nature of the fractions, as the monomeric TC-EI (a GA derivative) was least effective as compared to other fractions which were oligomeric, and the order of their effectiveness as per their IbD50 value being TC-EIV (8.9 micrograms)TC-EIII (17.8 micrograms)TC-EII (45 micrograms)TC-EI (320 micrograms) in TA98; TC-EIV being 40 times more effective than TC-EI in inhibiting his+ revertants. A similar effect was noticed in TA100 too, where TC-EI was the least effective and TC-EII had the maximum effect. A similar result was noticed when the antimutagenicity of GA (a monomeric) was compared with tannic acid (TA, an oligomeric). However, chebula tannins were found to be partly effective against NPD but not at all effective against 4NQNO.