Naphthalimide based novel organoselenocyanates: finding less toxic forms of selenium that would retain protective efficacy

A series of naphthalimide based organoselenocyanates were synthesized and screened for their toxicity as well as their ability to modulate several detoxifying/antioxidative enzyme levels at a primary screening dose of 3 mg/kg b.w. in normal Swiss albino mice for 30 days. Compound 4d showed highest activity in elevating the detoxifying/antioxidant enzymes levels.     

Preferential binding of fisetin to the native state of bovine serum albumin: spectroscopic and docking studies

We have investigated the binding of the biologically important flavonoid fisetin with the carrier protein bovine serum albumin using multi-spectroscopic and molecular docking methods. The binding constants were found to be in the order of 10⁴ M^?1 and the number of binding sites was determined as one. MALDI-TOF analyses showed that one fisetin molecule binds to a single bovine serum albumin (BSA) molecule which is also supported by fluorescence quenching studies. The negative Gibbs free energy change (?G°) values point to a spontaneous binding process which occurs through the presence of electrostatic forces with hydrophobic association that results in a positive entropy change (+51.69 ± 1.18 J mol^?1 K^?1). The unfolding and refolding of BSA in urea have been studied in absence and presence of fisetin using steady-state fluorescence and lifetime measurements. Urea denaturation studies indicate that fisetin is gradually released from its binding site on the protein. In the absence of urea, an increase in temperature that causes denaturation of the protein results in the release of fisetin from its bound state indicating that fisetin binds only to the native state of the protein. The circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopic studies showed an increase in % α-helix content of BSA after binding with fisetin. Site marker displacement studies in accordance with the molecular docking results suggested that fisetin binds in close proximity of the hydrophobic cavity in site 1 (subdomain IIA) of the protein. The PEARLS (Program of Energetic Analysis of Receptor Ligand System) has been used to estimate the interaction energy of fisetin with BSA and the results are in good correlation with the experimental findings.     

Evaluation of in vitro antifungal activity of medicinal plants against phytopathogenic fungi

Fourteen medicinal plants belonging to 13 families were collected and extracted with petroleum ether (PE), chloroform, methanol and water to yield 60 crude extracts. Using agar diffusion method, these extracts were evaluated for antifungal activity on the growth of five phytopathogenic fungi. Among all the extracts tested, PE, chloroform and methanol extracts of Piper betle L. and PE and chloroform extracts of Allamanda cathartica exhibited promising antifungal activity. Minimum inhibitory concentration (MIC) values of the above promising extracts were determined using broth dilution technique and observed that chloroform extract of P. betle L. exhibited the least MIC value ranging from 280 to 1130 μg ml^?1. In this study, we report chloroform extract of P. betle L. to be thermally stable even when steam sterilised for the first time and that it could be stored at 4°C with almost no change in its activity for a period of 180 days.     

FeCl3 mediated arylidenation of carbohydrates

Glycosides and thioglycosides based on monosaccharides in reaction with benzaldehyde dimethylacetal or p-methoxybenzaldehyde dimethyl acetal undergo FeCl₃-catalyzed (20 mol %) regioselective 4,6-O-arylidenation producing the corresponding acetals in high yields. FeCl₃ also mediates acetalation of glycosides and thioglycosides of cellobiose, maltose, and lactose affording the corresponding 4′,6′-O-benzylidene acetals, which were isolated after their acetylation in situ with acetic anhydride and pyridine. The combined yields (two steps) of these final products are also high (61–84%). The procedure is applicable to a wide variety of functional groups including –OBn.     

Graphene oxide-polyethylenimine nanoconstruct as a gene delivery vector and bioimaging tool

Graphene oxide (GO) has attracted an increasing amount of interest because of its potential applications in biomedical fields such as biological imaging, molecular imaging, drug/gene delivery, and cancer therapy. Moreover, GO could be fabricated by modifying its functional groups to impart specific functional or structural attributes. This study demonstrated the development of a GO-based efficient gene delivery carrier through installation of polyethylenimine, a cationic polymer, which has been widely used as a nonviral gene delivery vector. It was revealed that a hybrid gene carrier fabricated by conjugation of low-molecular weight branched polyethylenimine (BPEI) to GO increased the effective molecular weight of BPEI and consequently improved DNA binding and condensation and transfection efficiency. Furthermore, this hybrid material facilitated sensing and bioimaging because of its tunable and intrinsic electrical and optical properties. Considering the extremely high transfection efficiency comparable to that of high-molecular weight BPEI, high cell viability, and its application as a bioimaging agent, the BPEI-GO hybrid material could be extended to siRNA delivery and photothermal therapy.     

Evolutionary analysis of prokaryotic heat-shock transcription regulatory protein σ³²

Heat-stress to any living cell is known to trigger a universal defense response, called heat-shock response, with rapid induction of tens of different heat-shock proteins. Bacterial heat-shock genes are transcribed by the σ³²-bound RNA polymerase instead of the normal σ⁷⁰-bound RNA polymerase. In this study, the diversity in sequence, variation in secondary structure and function amongst the different functional regions of the proteobacterial σ³² family of proteins, and their phylogenetic relationships have been analyzed. Bacterial σ³² proteins can be subdivided into different functional regions which are referred to as regions 2, 3, and 4. There is a great deal of sequence conservation among the functional regions of proteobacterial σ³² family of proteins though some mutations are also present in these regions. Region 2 is the most conserved one, while region 4 has comparatively more variable sequences. In the present work, we tried to explore the effects of mutations in these regions. Our study suggests that the sequence diversities due to natural mutations in the different regions of proteobacterial σ³² family lead to different functions. So far, this study is the first bioinformatic approach towards the understanding of the mechanistic details of σ³² family of proteins using the protein sequence information only. This study therefore may help in elucidating the hitherto unknown molecular mechanism of the functionalities of σ³²family of proteins.     

Novel sterol metabolic network of Trypanosoma brucei procyclic and bloodstream forms

Trypanosoma brucei is the protozoan parasite that causes African trypanosomiasis, a neglected disease of people and animals. Co-metabolite analysis, labelling studies using [methyl-2H3]-methionine and substrate/product specificities of the cloned 24-SMT (sterol C24-methyltransferase) and 14-SDM (sterol C14demethylase) from T. brucei afforded an uncommon sterol metabolic network that proceeds from lanosterol and 31-norlanosterol to ETO [ergosta-5,7,25(27)-trien-3β-ol], 24-DTO [dimethyl ergosta-5,7,25(27)-trienol] and ergosterol [ergosta-5,7,22(23)-trienol]. To assess the possible carbon sources of ergosterol biosynthesis, specifically 13C-labelled specimens of lanosterol, acetate, leucine and glucose were administered to T. brucei and the 13C distributions found were in accord with the operation of the acetate-mevalonate pathway, with leucine as an alternative precursor, to ergostenols in either the insect or bloodstream form. In searching for metabolic signatures of procyclic cells, we observed that the 13C-labelling treatments induce fluctuations between the acetyl-CoA (mitochondrial) and sterol (cytosolic) synthetic pathways detected by the progressive increase in 13C-ergosterol production (control<[2-(13)C]leucine<[2-(13)C]acetate<[1-(13)C]glucose) and corresponding depletion of cholesta-5,7,24-trienol. We conclude that anabolic fluxes originating in mitochondrial metabolism constitute a flexible part of sterol synthesis that is further fluctuated in the cytosol, yielding distinct sterol profiles in relation to cell demands on growth.