Cytotoxic cobalt (III) Schiff base complexes: in vitro anti-proliferative, oxidative stress and gene expression studies in human breast and lung cancer cells.

Increasing cancer drug chemo-resistance, especially in the treatment of breast and lung cancers, alarms the immediate need of newer and effective anticancer drugs. Until now, chemotherapeutics based on metal complexes are considered the most effective treatment modality. In the present study, we have evaluated the cytotoxic effect of two cobalt (III) Schiff base complexes based on the leads from complex combinatorial chemistry. Cobalt (III) Schiff base complexes (Complex 3 = Co(Ph-acacen)(HA)2](ClO4) and Complex 4 =  [Co(Ph-acacen)(DA)2](ClO4)] (Ph-acacen, 1-phenylbutane-1,3-dione; DA, dodecyl amine; HA, heptylamine) were evaluated against human breast cancer cell MCF-7 and lung cancer cell A549 using MTT cell viability assay, cellular morphological changes studied by Acridine Orange and Ethidium Bromide (AO/EB), Dual fluorescent staining, Hoechst staining 33248, Comet assay, Annexin V-Cy3 and 6 CFDA assay, JC-1 staining, Reactive oxygen species (ROS) assay, Immunofluorescence assay, and Real-time reverse transcription-polymerase chain reaction (RT-qPCR). Treatment of cobalt (III) Schiff base complexes (Complex 3 & 4) affected the viability of the cancer cells. The cell death induced by the complexes was predominantly apoptosis, but necrosis also occurred to a certain extent. Complex 4 produced better cytotoxic effect than complex 3, and MCF-7 cell was more responsive than A549. In that order, the complexes were more selective to cancer cell than normal cell, and more effective in overall performance than the standard drug cisplatin. Therefore, we conclude that cobalt (III) Schiff base complexes, especially complex 4, have the potential to be developed as effective drugs for treatment of cancers in general, and breast and lung cancers in particular.

Enlightening the characteristics of bioflocculant of endophytic actinomycetes from marine algae and its biosorption of heavy metal removal.

The removal of toxic heavy metal ions from contaminated environments is a great challenge and requires an alternative rapid, efficient, economical bioremediation approach. Henceforth, bioflocculant producing endophytic actinobacterial sp. was isolated from heavy metal contaminated marine environments for heavy metal biosorption process. After molecular characterization, the isolated actinomycete starin was Nocardiopsis sp. GRG 3 (KT235642). It was indicated that the maximum flocculating activity of 80.90% with glucose, and yield is 4.52 g L1. The optimum flocculating activity was reached at pH 7 in the presence of CaCl2 ions. Further, the bioflocculent produced Nocardiopsis sp. GRG 3 (KT235642) was characterized by fourier transform infrared analysis spectra (FTIR) and displayed the presence of carboxyl, hydroxyl, amino groups and characteristic of more polysaccharide and protein. The heavy metal sorption by bioflocculant Nocardiopsis sp. GRG 3 (KT235642) was effectively removed 55.90% Cd, 85.90% Cr, 74.7% Pb, and 51.90% Hg. Therefore, this study was proved that the bioflocculant derived from endophytic actinobacteria, Nocardiopsis sp. GRG 3 (KT235642) as a effective alternative method for decreasing the heavy metals towards sustainable environmental management.

Potential application of two cobalt (III) Schiff base complexes in cancer chemotherapy: Leads from a study using breast and lung cancer cells.

Cobalt (III) Schiff base complexes are of attraction in the context of their potential application in cancer therapy. The aim of this study has been to find the mechanism of action of cobalt (III) Schiff base complexes 1 and 2, the synthesis and characterization of which have already been reported, in inhibiting growth of human breast cancer cell MCF-7 and lung cancer cell A549. The already proclaimed anti-proliferative effect of the cobalt complexes was ascertained using MTT cytotoxicity assay. More assays such as Acridine orange & Ethidium bromide staining, AnnexinV-Cy3 staining, Hoechst staining, comet assay, and Reactive Oxygen Species (ROS) assay- all supported the cytotoxic property of the complexes. Moreover, the expression levels of mRNA of pro- and antiapoptotic genes also supported the effectiveness of cobalt complexes by modifying the ratio of Bax: Bcl-2. In addition, the cobalt complexes induced apoptosis in MCF- 7 and A549 cells through modulation of pro-apoptotic, anti-apoptotic, and ROS modulatory gene expressions. The present study validates the scientific evidence for antiproliferative efficacy of cobalt complexes against MCF-7 and A549 cells. Thus, this study takes cobalt complexes 1 and 2 to a step higher towards their use as anticancer agents.

Evolving high-throughput approaches to assess the environmental risk of sewage water at molecular level: comprehensive study.

Dissolved organic matter (DOM) especially anthropogenic compounds in sewage systems affects their ultimate fate in the environment which is challenging to ascertain the heterogenic nature of the compound and causes co-occurring effects in most aquatic samples. So, our study have focused on current approaches to the chemical and structural characterization of DOM with the detailed classification of individual compounds such as the molecular levels of volatile organic, inorganic materials, drugs and endocrine disrupting compounds. Analytical techniques for example high performance gas chromatography-mass spectrometry (GCMS) with high-resolution liquid chromatography (HR-LCMS), X-ray diffraction (XRD) and three-dimensional fluorescence excitation emission matrix (3D-EEM) has resulted in advancing the parametric studies. In addition, the toxicological assessment of an aquatic organism (zebrafish as a model) has ensued in enlightening the risk of contaminated sources. The result of the research highlighted the efficacy of high-throughput approaches to assess the environmental impact of sewage water.

An overview of organic matters in municipal wastewater: Removal via self-assembly flocculating mechanism and the molecular level characterization.

On considering the critical issues in attaining stringent water quality standards and not creating any environmental impacts, we focused for the first time the economically feasible, emerging technology known as Self-assembly flocculating (Saf process). In which, the study investigated the applicability of bioflocculant (a biopolymer-self-assembly in nature) act as a surrogates on relying the removal of broad spectrum of substances under optimized conditions (Dosage: 90 mg/L; pH: 7; CaCl2). On using different techniques, the results have proved in removing the organic matter such as pharmaceuticals (Gentamycin, Cholecalciferol, Fluvoxamine, 3-OH Desogestrel, and Pheniramine), endocrine disturbing compounds [Phthalic acid, Benzene, 1, 2, 4 -Trimethoxy-5-(1-Propenyl)-, Benzene, 1, 2-Dimethoxy-4-(2-Propenyl)-, 1, 2-Benzenedicarboxylic Acid, 3-Cyclohexen-1-ol], fluorescent components (Polysaccharide like material), and others. The toxicological assessment of self-assembly bioflocculant implemented on zebra fish were statistically correlated [r = 0.95, p < 0.01 and 0.05 for P1WW; r = 0.91, p < 0.01 and 0.05 for P2WW] and [r = 0.7 5, p < 0.05 for P1WT; r = 0.095, p < 0.01 and 0.05 for P2WT]. This integrated approach supplemented further information of zeta potential (-16 mV in P1WW and -14.6 mV in P2WW decreased to -1.05 mV and -1.56 mV) with particle size distribution to explain via Saf process. In this research, the new insight has established non-toxic, self-assembly, biodegradable, bioflocculant for effective bioremediation.

Characterization of self-assembled bioflocculant from the microbial consortium and its applications.

Bioflocculant has been recently exploited in various research activities. In this research, we report for the first time that a novel bioflocculant can self-assemble into nanoparticles with an irregular structure in solution. Bioflocculant has been developed from novel consortium encompassing Enterococcus faecalis, Proteus mirabilis, Lysini bacillus sp., inoculated into the modified medium such as hydrolyzed wheat bran and rice bran extract. Characterization of bioflocculant shows that it is made up of mannose, fructose, raffinose, and galactose with a slightly negative charges. They are further characterized by FTIR and XPS. 3D-EEM and MALDITOF-MS are confirmed the proteoglycan nature of the bioflocculant. These bioflocculant not only exhibits greater biosorption of heavy metals by self-flocculating (or) self-aggregating activity, but also possesses mosquitocidal and anti-biofilm activity due to its cell surface modification. Further research have to be carried out regarding the mechanism of self-assembly nature of bioflocculant into nanoparticle in solution which provide a new path for bioremediation and biomedical application.

Dual drug loaded PLGA nanospheres for synergistic efficacy in breast cancer therapy.

Improved therapeutic effects can be achieved by the delivery of combination of drugs through multifunctional cell targeted nanocarrier systems. The present investigation reports the preparation of Poly (D,L-lactic-co-glycolic acid) (PLGA) nanospheres loaded with the novel combination such as Rutin (R) and Benzamide (B) as drugs using water-oil-water (w/o/w) emulsion method. Dual drug loaded PLGA nanospheres (R/B@PLGA) were stabilized by poly (vinyl alcohol) (PVA) coating and characterized in terms of morphology, size, surface charge, and structural chemistry by Scanning electron microscopy (SEM), Dynamic light scattering (DLS), Zeta potential analysis, UV-vis and Fourier transform infrared (FT-IR) spectroscopy. The inhibitory effects of rutin and benzamide on MDA-MB-231 (triple negative breast cancer-TNBC) cells using the drug loaded PLGA nanospheres as well as their non-toxic features were evaluated in vivo. The anticancer activity of the R/B@PLGA nanospheres through cell cycle disruption and apoptotic induction was assessed in vitro by flow cytometry analysis. Further, the in vitro antioxidant capacity, pH-based drug release and hemocompatible property were also investigated. It was shown that the R/B@PLGA nanospheres lacked genotoxic potential and they did not alter the antioxidant enzyme activities and histological features of zebrafish. Hence, this dual drug delivery system (DDS) not only actively targets multidrug-resistance (MDR) associated phenotype but also improves the therapeutic efficiency by its non-toxic nature towards enhanced cancer cell focused delivery and sustained release of therapeutic agents.

Antibacterial synergy between rutin and florfenicol enhances therapeutic spectrum against drug resistant Aeromonas hydrophila.

Emergence of antibiotic resistant bacteria has necessitated the drive to explore competent antimicrobial agents or to develop novel formulations to treat infections including Aeromonas hydrophila. The present study investigates the synergistic antibacterial effects of citrus flavonoid rutin and florfenicol (FF) against A. hydrophila in vitro and in vivo. Rutin is extracted and purified from Citrus sinensis peel through preparative HPLC and characterized through TLC, GC-MS and 1H and 13C NMR analyses. Though rutin did not display significant antibacterial activity, it modulated FF activity resulting in four-fold reduction in the MIC value for FF. The anti-biofilm potential of synergistic association of rutin and FF was validated by protein analysis, quantification of exopolysaccharide (EPS) and microscopy studies using sub-MIC doses. Besides antibacterial action, in vivo studies showed that Rutin/FF combination enhanced host immunity by improving blood cell count, anti-protease, and lysozyme activities as well as decreased the oxidative stress and the pathological changes of tilapia Oreochromis niloticus against A. hydrophila infection. No significant DNA damages or clastogenic effects were detected in tilapia challenged with A. hydrophila under Rutin/FF treatment. It is shown that an acute-phase Lipopolysaccharide binding protein (LBP) enhances the innate host defence against bacterial challenge. Semi quantitative RT-PCR and western blot results revealed the significant increase of LBP in the supernatant of tilapia monocytes/macrophages challenged with A. hydrophila upon treatment. The study findings substantiate that the combination of natural molecules with antibiotics may open up possibilities to treat MDR strains.

Optimization of reaction conditions to fabricate nano-silver using Couroupita guianensis Aubl. (leaf & fruit) and its enhanced larvicidal effect.

Currently bioactive principles of plants and their nanoproducts have been extensively studied in agriculture and medicine. In this study Couroupita guianensis Aubl. leaf and fruit extracts were selected for rapid and cost-effective synthesis of silver nanoparticles (leaf-LAgNPs and fruit-FAgNPs). Various physiological conditions such as temperature, pH, concentration of metal ions, stoichiometric proportion of reaction mixture and reaction time showed influence on the size, dispersity and synthesis rate of AgNPs. Generation of AgNPs was initially confirmed with the surface plasmon vibrations at 420 nm in UV-visible spectrophotometer. The results recorded from X-ray diffractometer (XRD) and Transmission electron microscope (TEM) supports the biosynthesis of cubic crystalline LAgNPs & FAgNPs with the size ranges between 10-45 nm and 5-15 nm respectively. Surface chemistry of synthesized AgNPs was studied with Fourier transform infrared spectroscopy (FTIR), it reveals that water soluble phenolic compounds present in the extracts act as reducing and stabilizing agent. Leaf, fruit extracts and synthesized AgNPs were evaluated against IV instar larvae of Aedes aegypti (Diptera; Culicidae). Furthermore, different extracts and synthesized AgNPs showed dose dependent larvicidal effect against A. aegypti after 24h of treatment. Compare to all extracts such as ethyl acetate (leaf; LC50 - 44.55 ppm and LC90 - 318.39 ppm & fruit; LC50 - 49.96 ppm and LC90 - 568.84 ppm respectively) and Methanol (leaf; LC50 - 85.75 ppm and LC90 - 598.63 ppm & fruit; LC50 - 67.78 ppm and LC90 - 714.45 ppm respectively) synthesized AgNPs showed extensive mortality rate (LAgNPs; LC50 - 2.1 ppm and LC90 - 5.59 ppm & FAgNPs; LC50 - 2.09 ppm and LC90 - 5.7 ppm). Hence, this study proves that C. guianensis is a potential bioresource for stable, reproducible nanoparticle synthesis (AgNPs) and also can be used as an efficient mosquito control agent.