Anticancer potential of AgNPs synthesized using Acinetobacter sp. and Curcuma aromatica against HeLa cell lines: A comparative study.

BACKGROUND: Biogenic nanoparticles are gaining attention due to their low toxicity and numerous biomedical applications. Present study aimed to compare the potential anticancer activity of two biogenic silver nanoparticles (bAgNPs and pAgNPs) against human cervical cancer cell lines (HeLa). METHODS: bAgNPs were synthesized using Acinetobacter sp. whereas pAgNPs were synthesized using aqueous root extract of Curcuma aromatica. Effect of these nanoparticles on HeLa cells viability was studied using MTT assay and colony formation assay. Anticancer potential was determined using fluorescence microscopy and flow cytometry studies. Bio-compatibility studies were performed against peripheral blood mononuclear cells (PBMCs). RESULTS: Both the nanoparticles showed 50 % viability of peripheral blood mononuclear cells (PBMCs) when used at high concentration (200 µg/mL). IC50 for bAgNPs and pAgNPs against HeLa cells were 17.4 and 14 µg/mL respectively. Colony formation ability of Hela cells was reduced on treatment with both nanoparticles. Acridine orange and ethidium bromide staining demonstrated that bAgNPs were cytostatic whereas pAgNPs were apoptotic. JC-1 dye staining revealed that the mitochondrial membrane potential was affected on treatment with pAgNPs while it remained unchanged on bAgNPs treatment. Flow cytometry confirmed cell cycle arrest in HeLa cells on treatment with nanoparticles further leading to apoptosis in case of pAgNPs. About 77 and 58 % HeLa cells were found in subG1 phase on treatment with bAgNPs and pAgNPs respectively. bAgNPs showed cytostatic effect on HeLa cells arresting the cell growth in subG1 phase, whereas, pAgNPs triggered death of HeLa cells through mitochondrial membrane potential impairment and apoptosis. CONCLUSION: Overall, bAgNPs and pAgNPs could be safe and showed potential to be used as anticancer nano-antibiotics against human cervical cancer cells.

Green Synthesis of AuNPs by Acinetobacter sp. GWRVA25: Optimization, Characterization, and Its Antioxidant Activity.

Bacteriogenic synthesis of metal nanoparticles is ecofriendly and greatly influenced by physico-chemical reaction parameters with respect to shape and size. Thus, present work aimed to synthesize and optimization of bacteriogenic gold nanoparticles (AuNPs) and study their antioxidant activity. Acinetobacter sp. cells were able to synthesize AuNPs, when challenged with tetra-chloroauric acid (HAuCl4). By physicochemical optimization, maximum synthesis was obtained with 72 h old culture using 2.1 × 109 CFU/ml cell density. Whereas, pH-7 is suitable for AuNPs synthesis. HAuCl4 concentration (0.5 mM) enhanced the formation of monodispersed and spherical nanoparticles (15 ± 10 nm). At 37°C temperature, Acinetobacter sp. released nanoparticles in supernatant. From characterization, AuNPs were found to be crystalline in nature with negative surface charge. AuNPs showed up to 86% different radical scavenging ability, exhibiting antioxidant activity. In conclusion, spherical AuNPs can be synthesized using Acinetobacter sp. through physicochemical optimization. This is the first report of antioxidant activity exhibited by monodispersed bacteriogenic AuNPs synthesized using Acinetobacter sp.

Antibacterial Activities of Bacteriagenic Silver Nanoparticles Against Nosocomial Acinetobacter baumannii.

Acinetobacter baumannii has emerged as one of the major nosocomial pathogens implicated in variety of severe infections and mortality. It is rapidly developing multi-drug resistance and also possesses surface colonization ability, which make it most difficult to treat through traditional antibiotics. This is an extensive study to describe the antibacterial activity of bacteriagenic silver nanoparticles (AgNPs) against A. baumannii AIIMS 7 in planktonic and biofilm mode. Minimum inhibitory concentration of antibiotics were in the range of 1 to 4096 µg/ml whereas AgNPs inhibited planktonic bacteria at concentration of 16 µg/ml. Fractional inhibitory concentration index revealed the synergistic interaction of AgNPs with doxycycline, tetracycline and erythromycin. Nanoparticles exhibited significant biofilm disruption activity with minimum biofilm eradication concentration of 2 mg/ml. Eradication of mature biofilm was enhanced on exposure to combination of AgNPs and antibiotics. These nanoparticles affected bacterial growth and distorted cellular morphology. Intracellular oxidative stress, induced in presence of AgNPs, also rendered bacteria susceptible to killing by nanoparticles. Besides this, AgNPs were found to interact with thiol-groups, which indicate their potential to interact with cellular proteins to exhibit antimicrobial activity.

Biosynthesis of gold and selenium nanoparticles by purified protein from Acinetobacter sp. SW 30.

Synthesis of nanoparticles is an enzymatic reduction process in microorganisms. In the present study, a protein, lignin peroxidase has been purified by DEAE-Cellulose anion exchange chromatography and Biogel P-150 gel filtration chromatography from the cell suspension of Acinetobacter sp. SW30 responsible for the synthesis of gold nanoparticles (AuNP) and selenium nanoparticles (SeNP). The purified fraction has a specific activity of 29.4U/mg/min with 959 fold purification. Native and SDS PAGE confirmed that purified lignin peroxidase is monomeric enzyme with 97.4KDa molecular weight. The enzyme synthesized spherical crystalline AuNP (10±2nm) and amorphous SeNP (100±10nm). It has maximum activity at pH 2 and temperature 40°C, with 1.0mMKm value, when n-propanol was used as a substrate. Activity was completely inhibited by sodium thiosulphate and zinc sulphate. This is the first report on association of lignin peroxidase in the synthesis of AuNP and SeNP from Acinetobacter sp. SW30.

Lignin peroxidase mediated silver nanoparticle synthesis in Acinetobacter sp.

Metals present in environment render the bacteria to attain certain resistance machinery to survive, one of which is transformation of metal ions to nano forms. Various enzymes and proteins have been suggested to play significant role in synthesis of silver nanoparticles (AgNPs) in bacteria. In present study, we have purified lignin peroxidase from secreted enzyme extract of Acinetobacter sp. employing diethyl aminoethyl cellulose ion exchange and Biogel P-150 gel filtration column chromatography. The purified fraction has a specific activity of 1.571 U/mg with substrate n-propanol and 6.5-fold purification. The tetrameric enzyme, with molecular weight of 99 kDa, consisted of dimers of two polypetides of 23.9 and 24.6 kDa as revealed by native and SDS-PAGE. On exposure to purified enzyme, spherical polydispersed AgNPs of ~ 50 nm were obtained as observed under transmission electron microscope. Optimum activity of the purified enzyme was obtained at pH 2 and 60 °C with n-propanol as substrate. This is the first report describing the reduction of extracellular silver ions by lignin peroxidase purified from Acinetobacter sp.

Green synthesis of selenium nanoparticles using Acinetobacter sp. SW30: optimization, characterization and its anticancer activity in breast cancer cells.

The aim of this study was to synthesize selenium nanoparticles (SeNPs) using cell suspension and total cell protein of Acinetobacter sp. SW30 and optimize its synthesis by studying the influence of physiological and physicochemical parameters. Also, we aimed to compare its anticancer activity with that of chemically synthesized SeNPs in breast cancer cells. Cell suspension of Acinetobacter sp. SW30 was exposed to various physiological and physicochemical conditions in the presence of sodium selenite to study their effects on the synthesis and morphology of SeNPs. Breast cancer cells (4T1, MCF-7) and noncancer cells (NIH/3T3, HEK293) were exposed to different concentrations of SeNPs. The 18 h grown culture with 2.7×109 cfu/mL could synthesize amorphous nanospheres of size 78 nm at 1.5 mM and crystalline nanorods at above 2.0 mM Na2SeO3 concentration. Polygonal-shaped SeNPs of average size 79 nm were obtained in the supernatant of 4 mg/mL of total cell protein of Acinetobacter sp. SW30. Chemical SeNPs showed more anticancer activity than SeNPs synthesized by Acinetobacter sp. SW30 (BSeNPs), but they were found to be toxic to noncancer cells also. However, BSeNPs were selective against breast cancer cells than chemical ones. Results suggest that BSeNPs are a good choice of selection as anticancer agents.

Kinetics of Synthesis of Gold Nanoparticles by Acinetobacter sp. SW30 Isolated from Environment.

Cell biomass and metal salt concentration have great influence on morphology of biosynthesized nanoparticle. The aim of present study was to evaluate the effect of varying cell density and gold salt concentrations on synthesis of nanoparticles and its morphology, which has not been studied in bacteria till now. When cells of Acinetobacter sp. SW30 were incubated with different cell density and gold chloride concentrations, tremendous variation in color of colloidal solution containing gold nanoparticles (AuNP) was observed indicating variation in their size and shapes. Surprisingly, monodispersed spherical AuNP of size ~19 nm were observed at lowest cell density and HAuCl4 salt concentration while increase in cell number resulted in formation of polyhedral AuNP (~39 nm). Significance of this study lays in the fact that the shape and dispersity of AuNP can be customized depending up on the requirement. FTIR spectrum revealed shift from 3221 to 3196 cm-1 indicating the presence and role of amino acids in Au3+ reduction while possible involvement of amide I and II groups in stabilization of AuNP. The rate constant was calculated for cell suspension of 2.1 × 109 cfu/ml challenged with 1.0 mM HAuCl4, incubated at 30 °C and pH 7 using the slopes of initial part of the plot log (Aα - At) versus time as 1.99 × 10-8 M. Also, this is the first study to report the kinetics of gold nanoparticle synthesis by Acinetobacter sp. SW30.

Biogenic selenium nanoparticles: current status and future prospects.

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicine owing to their antibacterial and anticancer properties. SeNPs are biocompatible and non-toxic compared to the counterparts, selenite (SeO3 (-2)) and selenate (SeO4 (-2)). They can be synthesized by physical, chemical, and biological methods and have distinct bright orange-red color. Biogenic SeNPs are stable and do not aggregate owing to natural coating of the biomolecules. Various hypotheses have been proposed to describe the mechanism of microbial synthesis of SeNPs. It is primarily a two-step reduction process from SeO4 (-2) to SeO3 (-2) to insoluble elemental selenium (Se(0)) catalyzed by selenate and selenite reductases. Phenazine-1-carboxylic acid and glutathione are involved in selenite reduction. Se factor A (SefA) and metalloid reductase Rar A present on the surface of SeNPs confer stability to the nanoparticles. SeNPs act as potent chemopreventive and chemotherapeutic agents. Conjugation with antibiotics enhances their anticancer efficacy. These also have applications in nanobiosensors and environmental remediation.

Diosgenin Functionalized Iron Oxide Nanoparticles as Novel Nanomaterial Against Breast Cancer.

Iron oxide nanoparticles (IONPs) have gained immense importance recently as drug nanocarriers due to easy multifunctionalization, simultaneous targeting, imaging and cancer hyperthermia. Herein, we report a novel nanomedicine comprising of IONPs core functionalized with a potent anticancer bioactive principle, diosgenin from medicinal plant Dioscorea bulbifera via citric acid linker molecule. IONPs were synthesized by reverse co-precipitation and characterized using field emission scanning electron microscopy (FESEM), high resolution transmission electron microscopy (HRTEM) and dynamic light scattering (DLS). Diosgenin functionalization was confirmed using fourier transform infrared spectroscopy (FTIR) and biochemical methods. Synthesized IONPs, citrate linked IONPs (IONPs-CA), diosgenin functionalized IONPs (IONPs-D) along with free citric acid and diosgenin were checked for anticancer activity against MCF7 breast cancer cells by MTT assay, wound migration assay, confocal microscopy and protein expression by western blotting. Size of IONPs, IONPs-CA and IONPs-D gradually increased ranging from 12 to 21 nm as confirmed by FESEM and HRTEM. Signature peaks of diosgenin at 2914, 1166 and 1444 cm-1 IONPs-D, revealed in FTIR indicated the presence of functionalized diosgenin. IONPs-D exhibited 51.08 ± 0.37% antiproliferative activity against MCF7 cells, which was found to be superior to free citric acid (17.71 ± 0.58%) and diosgenin (33.31 ± 0.37%). Treatment with IONPs-D exhibited reduced wound migration upto 40.83 ± 2.91% compared to bare IONPs (89.03 ± 2.58%) and IONPs-CA (50.35 ± 0.48%). IONPs-D and diosgenin exhibited apoptosis induction, confirmed by Alexa Fluor 488 annexin V/PI double-stained cells indicating extensive cell membrane damage coupled with PI influx leading to nuclear staining in treated cells. IONPs-D mediated selective PARP cleavage strongly rationalized it as superior apoptotic inducers. Based on these findings, IONPs-D can be considered as first diosgenin functionalized novel magnetic nanomedicine with antiproliferative, migration inhibiting and apoptosis inducing properties against breast cancer.

Curcumin-Loaded, Self-Assembled Aloevera Template for Superior Antioxidant Activity and Trans-Membrane Drug Release.

Fine combination of natural botanical extracts to evaluate and maximize their medicinal efficacy has been studied for long. However, their limited shelf-life, complicated extraction protocols, and difficult compositional analysis have always been a problem. It is due to this that such materials take time to convert them into a proper pharmaceutical technology or product. In this context, we report on synthesis of self-assembled template of one of the most popular natural product, aloevera. This forms a fine porous membrane like structure, in which a natural drug, curcumin has been immobilized/trapped. The so-made curcumin-loaded-aloevera (CLA) structures have been carefully evaluated using Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), atomic force microscopy (AFM), UV-vis spectroscopy and fluorescence microscopy. While FTIR shows that there is no chemical interaction between aloevera and curcumin, the pores are finely occupied by curcumin molecules. Fine microscopy structures reveal their distribution and fluorescence microscopy confirm the presence of curcumin within the pores. TGA shows 15% loading of the curcumin in the template and UV-visible spectroscopy data shows independent peaks of both, aloevera (196 nm and 256 nm) and curcumin (423 nm), respectively. When subjected to antioxidant studies, using DPPH assays, CLAs show a synergistically superior DPPH radical scavenging activity as compared to only curcumin and only aloevera extract. Same is true for hydroxyl and NO2 radicals. Trans-membrane release study reveals that there is no significant difference in the amount of curcumin release from CLAs till initial 30 min, however, it increases steadily thereafter. CLA is found to facilitate efficient release of curcumin in 5 h, which is higher as compared to the curcumin alone.

ZnO Nanoparticles-Red Sandalwood Conjugate: A Promising Anti-Diabetic Agent.

With the advances in nanoscience and nanotechnology the interest of researchers has expanded to interdisciplinary domain like bio-medical applications. Among such domains, one of the most important areas explored meticulously is the development of promising solutions in diabetes therapeutics. The disease associated with metabolic disorder, is one of the major challenges, due to its ever-increasing number of patients. The adverse effects of the synthetic enzymes like α-amylase and α-glucosidase inhibitors have invited many scientists to develop promising contender with minimal side-effects. On the other hand, Zinc has strong role in insulin synthesis, storage and secretion and thus its deficiency can be related to diabetes. In this context we have explored natural extract of Red Sandalwood (RSW) as a potent anti-diabetic agent, in conjugation with ZnO nanoparticles. ZnO nanoparticles have been synthesized via soft chemistry routes and duly characterized for their phase formation with the help of X-ray diffraction technique and Field-Emission Scanning Electron Microscopy. These monodispersed nanoparticles, -20 nm in size, were further conjugated to RSW extract. The conjugation chemistry was studied via Fourier transform infrared spectroscopy, UV-visible spectroscopy. Extract loading percentage was found from thermo-gravimetric analysis. 65% of the RSW extract was found conjugated to the ZnO nanoparticles. The anti-diabetic activity was assessed with the help of like α-amylase and α-glucosidase inhibition assay with murine pancreatic and small intestinal extracts. It was observed that the conjugated ZnO-RSW nanoparticles showed excellent activity against the crude murine pancreatic glucosidase as compared to the individual ZnO nanoparticles and the RSW extract. The ZnO-RSW conjugate showed 61.93% of inhibition while the bare ZnO nanoparticles and RSW showed 21.48% and 5.90% respectively.

Bacteriagenic silver nanoparticles: synthesis, mechanism, and applications.

Silver nanoparticles (AgNPs) have received tremendous attention due to their significant antimicrobial properties. Large numbers of reports are available on the physical, chemical, and biological syntheses of colloidal AgNPs. Since there is a great need to develop ecofriendly and sustainable methods, biological systems like bacteria, fungi, and plants are being employed to synthesize these nanoparticles. The present review focuses specifically on bacteria-mediated synthesis of AgNPs, its mechanism, and applications. Bacterial synthesis of extra- and intracellular AgNPs has been reported using biomass, supernatant, cell-free extract, and derived components. The extracellular mode of synthesis is preferred over the intracellular mode owing to easy recovery of nanoparticles. Silver-resistant genes, c-type cytochromes, peptides, cellular enzymes like nitrate reductase, and reducing cofactors play significant roles in AgNP synthesis in bacteria. Organic materials released by bacteria act as natural capping and stabilizing agents for AgNPs, thereby preventing their aggregation and providing stability for a longer time. Regulation over reaction conditions has been suggested to control the morphology, dispersion, and yield of nanoparticles. Bacterial AgNPs have anticancer and antioxidant properties. Moreover, the antimicrobial activity of AgNPs in combination with antibiotics signifies their importance in combating the multidrug-resistant pathogenic microorganisms. Multiple microbicidal mechanisms exhibited by AgNPs, depending upon their size and shape, make them very promising as novel nanoantibiotics.

Chemical and biological metal nanoparticles as antimycobacterial agents: A comparative study.

Resistance among mycobacteria leading to multidrug-resistant and extensively drug-resistant tuberculosis is a major threat. However, nanotechnology has provided new insights in drug delivery and medicine development. This is the first comparative report to determine the activity of chemically and biologically synthesised silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) against mycobacteria. Screening data revealed the high mycobactericidal efficiency of AgNPs, with minimum inhibitory concentrations (MICs) of <3µg/mL, whereas no such activity was exhibited by AuNPs at concentrations up to 100µg/mL. Moreover, in vitro and ex vivo THP-1 infection model assays showed greater efficacy of chemical AgNPs compared with biogenic AgNPs to inhibit active and dormant stage mycobacterial growth. Up to 40% cytotoxicity against human cell lines was observed at a AgNP concentration of 10× MIC (30µg/mL) after 48h. AgNPs were shown to have more specificity towards mycobacteria than towards other Gram-negative and Gram-positive pathogenic bacteria. The selectivity index was found to be in the range of 11-23, indicating the potential of these nanoparticles for use in developing new therapeutics for tuberculosis.

Dual drug conjugated nanoparticle for simultaneous targeting of mitochondria and nucleus in cancer cells.

Effective targeting of mitochondria has emerged as an alternative strategy in cancer chemotherapy. However, considering mitochondria's crucial role in cellular energetics, metabolism and signaling, targeting mitochondria with small molecules would lead to severe side effects in cancer patients. Moreover, mitochondrial functions are highly dependent on other cellular organelles like nucleus. Hence, simultaneous targeting of mitochondria and nucleus could lead to more effective anticancer strategy. To achieve this goal, we have developed sub 200 nm particles from dual drug conjugates derived from direct tethering of mitochondria damaging drug (α- tocopheryl succinate) and nucleus damaging drugs (cisplatin, doxorubicin and paclitaxel). These dual drug conjugated nanoparticles were internalized into the acidic lysosomal compartments of the HeLa cervical cancer cells through endocytosis and induced apoptosis through cell cycle arrest. These nanoparticles damaged mitochondrial morphology and triggered the release of cytochrome c. Furthermore, these nanoparticles target nucleus to induce DNA damage, fragment the nuclear morphology and damage the cytoskeletal protein tubulin. Therefore, these dual drug conjugated nanoparticles can be successfully used as a platform technology for simultaneous targeting of multiple subcellular organelles in cancer cells to improve the therapeutic efficacy of the free drugs.

Surface defect rich ZnO quantum dots as antioxidants inhibiting α-amylase and α-glucosidase: a potential anti-diabetic nanomedicine.

Preventing chronic hyperglycaemia and associated oxidative stress is utmost important for the treatment and management of Type 2 Diabetes Mellitus (T2DM). Here we report the role of different size surface defect rich ZnO quantum dots (D-QDs) for inhibiting metabolic enzymes and scavenging free radicals, which plays a key role in reducing hyperglycaemia and oxidative stress. Quantitative analysis of radical scavenging and metabolic enzyme inhibition activity of D-QDs demonstrates a size dependent behaviour, where D-QDs with a smaller diameter shows superior activity compared to larger size D-QDs. Considering the size dependence in surface defect formation, the increased surface defect density in smaller size D-QDs can be considered as the reason behind this enhancement. Detailed studies establishing the underlying mechanism behind potent free radical scavenging and enzyme inhibition provides an intense scientific rationale for considering D-QDs to design safe and effective nanomedicine for T2DM.

Novel platinum-palladium bimetallic nanoparticles synthesized by Dioscorea bulbifera: anticancer and antioxidant activities.

Medicinal plants serve as rich sources of diverse bioactive phytochemicals that might even take part in bioreduction and stabilization of phytogenic nanoparticles with immense therapeutic properties. Herein, we report for the first time the rapid efficient synthesis of novel platinum-palladium bimetallic nanoparticles (Pt-PdNPs) along with individual platinum (PtNPs) and palladium (PdNPs) nanoparticles using a medicinal plant, Dioscorea bulbifera tuber extract (DBTE). High-resolution transmission electron microscopy revealed monodispersed PtNPs of size 2-5 nm, while PdNPs and Pt-PdNPs between 10 and 25 nm. Energy dispersive spectroscopy analysis confirmed 30.88% ± 1.73% elemental Pt and 68.96% ± 1.48% elemental Pd in the bimetallic nanoparticles. Fourier transform infrared spectra indicated strong peaks at 3,373 cm(-1), attributed to hydroxyl group of polyphenolic compounds in DBTE that might play a key role in bioreduction in addition to the sharp peaks at 2,937, 1,647, 1,518, and 1,024 cm(-1), associated with C-H stretching, N-H bending in primary amines, N-O stretching in nitro group, and C-C stretch, respectively. Anticancer activity against HeLa cells showed that Pt-PdNPs exhibited more pronounced cell death of 74.25% compared to individual PtNPs (12.6%) or PdNPs (33.15%). Further, Pt-PdNPs showed an enhanced scavenging activity against 2,2-diphenyl-1-picrylhydrazyl, superoxide, nitric oxide, and hydroxyl radicals.

Characterization of the algC gene expression pattern in the multidrug resistant Acinetobacter baumannii AIIMS 7 and correlation with biofilm development on abiotic surface.

Relative quantification of algC gene expression was evaluated in the multidrug resistant strain Acinetobacter baumannii AIIMS 7 biofilm (3 to 96 h, on polystyrene surface) compared to the planktonic counterparts. Comparison revealed differential algC expression pattern with maximum 81.59-fold increase in biofilm cells versus 3.24-fold in planktonic cells (P < 0.05). Expression levels strongly correlated with specific biofilm stages (scale of 3 to 96 h), coinciding maximum at initial surface attachment stage (9 h) and biofilm maturation stage (48 h). Cloning, heterologous expression, and bioinformatics analyses indicated algC gene product as the bifunctional enzyme phosphomannomutase/phosphoglucomutase (PMM/PGM) of ∼ 53 kDa size, which augmented biofilms significantly in algC clones compared to controls (lacking algC gene), further localized by scanning electron microscopy. Moreover, molecular dynamics analysis on the three-dimensional structure of PMM/PGM (simulated up to 10 ns) revealed enzyme structure as stable and similar to that in P. aeruginosa (synthesis of alginate and lipopolysaccharide core) and involved in constitution of biofilm EPS (extracellular polymeric substances). Our observation on differential expression pattern of algC having strong correlation with important biofilm stages, scanning electron-microscopic evidence of biofilm augmentation taken together with predictive enzyme functions via molecular dynamic (MD) simulation, proposes a new basis of A. baumannii AIIMS 7 biofilm development on inanimate surfaces.

γ-Hydroxyethyl piperidine iminosugar and N-alkylated derivatives: a study of their activity as glycosidase inhibitors and as immunosuppressive agents.

An efficient and practical strategy for the synthesis of (3R,4s,5S)-4-(2-hydroxyethyl) piperidine-3,4,5-triol and its N-alkyl derivatives 8a-f, starting from the D-glucose, is reported. The chiral pool methodology involves preparation of the C-3-allyl-α-D-ribofuranodialdose 10, which was converted to the C-5-amino derivative 11 by reductive amination. The presence of C-3-allyl group gives an easy access to the requisite hydroxyethyl substituted compound 13. Intramolecular reductive aminocyclization of C-5 amino group with C-1 aldehyde provided the γ-hydroxyethyl substituted piperidine iminosugar 8a that was N-alkylated to get N-alkyl derivatives 8b-f. Iminosugars 8a-f were screened against glycosidase enzymes. Amongst synthetic N-alkylated iminosugars, 8b and 8c were found to be α-galactosidase inhibitors while 8d and 8e were selective and moderate α-mannosidase inhibitors. In addition, immunomodulatory activity of compounds 8a-f was examined. These results were substantiated by molecular docking studies using AUTODOCK 4.2 programme.

Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase.

Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

Novel polyhedral gold nanoparticles: green synthesis, optimization and characterization by environmental isolate of Acinetobacter sp. SW30.

Gold nanoparticles have enormous applications in cancer treatment, drug delivery and nanobiosensor due to their biocompatibility. Biological route of synthesis of metal nanoparticles are cost effective and eco-friendly. Acinetobacter sp. SW 30 isolated from activated sewage sludge produced cell bound as well as intracellular gold nanoparticles when challenged with HAuCl4 salt solution. We first time report the optimization of various physiological parameters such as age of culture, cell density and physicochemical parameters viz HAuCl4 concentration, temperature and pH which influence the synthesis of gold nanoparticles. Gold nanoparticles thus produced were characterized by various analytical techniques viz. UV-Visible spectroscopy, X-ray diffraction, cyclic voltammetry, transmission electron microscopy, selected area electron diffraction, high resolution transmission electron microscopy, environmental scanning electron microscopy, energy dispersive X-ray spectroscopy, atomic force microscopy and dynamic light scattering. Polyhedral gold nanoparticles of size 20 ± 10 nm were synthesized by 24 h grown culture of cell density 2.4 × 10(9) cfu/ml at 50 °C and pH 9 in 0.5 mM HAuCl4. It was found that most of the gold nanoparticles were released into solution from bacterial cell surface of Acinetobacter sp. at pH 9 and 50 °C.