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Potentiation of the antitumor effect of 11-keto-β-boswellic acid by its 3-α-hexanoyloxy derivative
No full textWe recently discovered that a propionyloxy derivative of 11-keto-β-boswellic acid (PKBA) showed better anticancer potential than other boswellic acids including AKBA, encompassing the importance of acyl group at the 3-α-hydroxy position of KBA. In continuation of our previous work, other higher derivatives (with increasing alkoxy chain length at 3-α-hydroxy position) including butyryloxy (BKBA) and hexanoyloxy(HKBA) derivatives of KBA were synthesized. The respective IC50 values of BKBA and HKBA in HL-60 cells were found to be 7.7 and 4.5 μg/ml. IC50 value of HKBA was comparatively lower than that of BKBA, and further lower than that of the previously reported derivative (PKBA, IC50 8.7 μg/ml). In order to compare the anticancer potential of HKBA with PKBA, detailed in vitro pro-apoptotic and in vivo anticancer studies were carried out. The induction of apoptosis by HKBA was measured using various parameters including
fluorescence and scanning electron microscopy, DNA fragmentation and Annexin V-FITC binding. The extent
of DNA damage was measured using neutral comet assay. HKBA was further evaluated for its effect on DNA cell cycle and mitochondria where it was found to arrest cells in G2/M phase and also induced loss of mitochondrial membrane potential. These events were associated with increased expression of cytosolic cytochrome c and cleavage of PARP. Target based studies showed that HKBA inhibited the enzymatic activity of topoisomerases I and II at low doses than that of PKBA. In vivo studies also revealed a low dose inhibitory effect of HKBA on ascitic and solid murine tumor models
In vitro antifungal activities of amphotericin B in combination with acteoside, a phenylethanoid glycoside from Colebrookea oppositifolia
No full textThis study was undertaken to investigate the synergistic interaction between amphotericin B(AmB) and acteoside, isolated from the aerial parts of the shrub Colebrookea oppositifolia(Lamiaceae). Acteoside alone exhibited no intrinsic antifungal activity but showed a potent
synergism in combination with AmB against selected pathogenic species, with fractional inhibitory concentration indices in the range of 0.0312–0.1562. The combination of acteoside at 3.12 and 12.5 mg ml–1 with subinhibitory concentrations of AmB resulted in a potent fungicidal effect and also exhibited a significantly extended post-antifungal effect. Furthermore, the combination also reduced the minimum biofilm reduction concentration values of AmB (2–16-fold) in preformed
biofilms of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. There was decreased viability of the cells, increased uptake of propidium iodide and enhanced leakage of 260 nm-absorbing material by Candida albicans cells when exposed to AmB in the presence of acteoside. The reason for potentiation is likely to be that the subinhibitory concentrations of AmB facilitated the uptake of acteoside, which resulted in increased killing of the fungal cells.Administration of acteoside in mice at up to 2000 mg (kg body weight)”1 by the intraperitoneal or
oral route produced no overt toxicity. The data presented here support synergism between acteoside and AmB, and it is therefore proposed that a prospective new management strategy for therapeutic application of this combination should be explored
Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain:in vitrocharacterisation
No full textPolymer-based nanotechnologies are proposed to be an alternative for drug administration, delivery and targeting to those of conventional formulations. The blood brain barrier is frequently a rate-limiting factor in determining permeation of a drug into brain. In this study, the surface-engineered long-circulating PLGA nanoparticles (NPs) were assessed for brain-specific delivery. Long circulating NPs of PLGA- and PEG-synthesised copolymer were prepared by emulsification solvent evaporation method. Further, the
surface of PEGylated NPs was modified by anchoring transferrin (Tf) ligand for receptor-mediated targeting
to brain. NPs were characterised for shape and size, zeta potential, entrapment efficiency and in vitro drug release. In vitro cytotoxicity studies were performed on human cancer cell lines. Confocal Laser Scanning Microscopy studies show the enhanced uptake of Tf-appended PEGylated NPs and their localisation in the brain tissues. Hence, the specific role of Tf ligand on PEGylated NPs for brain delivery was confirmed
A cyano analogue of boswellic acid induces crosstalk between p53/PUMA/Bax and telomerase that stages the human papillomavirus type 18 positive HeLa cells to apoptotic death
No full textThe p53 tumor suppressor pathway is disrupted by human papillomavirus (HPV) in over 90% of cervical
cancers. HPV E6 protein promotes the degradation of p53 thereby inhibiting its stabilization and activation.
This study demonstrates that treatment with a novel cyano derivative of 11-keto-;2-boswellic acid, i.e. butyl 2-
cyano-3, 11-dioxours-1,12-dien-24-oate (BCDD) reduced the viral E6 mRNA expression and lead to the accumulation of transcriptionally active p53 in the nucleus of HPV18 HeLa cells following DNA damage.Western blot analysis showed that BCDD robustly up regulated time-dependent expression of p53/PUMA/p21 whereas it deprived cells essentially of p-AKT and NF-;AB cell survival signalling cascade. BCDD appeared to gear up PUMA activation through p53 pathway and that both p53 and p21 translocated heavily into the nucleus. Simultaneously, it inhibited anti-apoptotic Bcl-2, augumented Drp-1 expression, disrupted mitochondrial functions causing the activation of proapoptotic proteins and caspases activation. Additionally,BCDD inhibited telomerase expression that's likely to result in a marked reduction of the tumorigenic potential of high-grade cervical cancers. Consequently BCDD caused apoptotic death in cervical cancer cells as evidenced by DNA fragmentation and PARP-cleavage. Further, BCDD did not affect the extrinsic signalling transduction pathway as depicted by its null effect on caspase-8. The in vivo anticancer activity of BCDD was investigated in Ehrlich Ascites carcinoma model where it exhibited tumor regression by 48% at 30 mg/kg, i.p.,in mice. These findings indicated that BCDD is a potential candidate that may be found useful in the management of cervical cancer
Iron oxide mediated direct C–H arylation/alkylation at α-position of cyclic aliphatic ethers
No full textWe report a new and efficient iron oxide catalyzed crosscoupling reaction between organometallic species such as
alkyl/arylmagnesium halides or organolithium species and
a-hydrogen bearing cyclic aliphatic ethers via activation of
C(sp3)–H. This is the first example of iron oxide mediated direct C–C bond formation without expensive or toxic ligands
Psilostachyin, acetylated pseudoguaianolides and their analogues: Preparation and evaluation of their anti-inflammatory potential
No full textNaturally occurring acetylated pseudoguaianolides and psilostachyin including their analogues were synthesized.
The structure of semi-synthetic psilostachyin was also confirmed by X-ray crystallography. The anti-inflammatory potential of all the derivatives has been evaluated through in vitro expression of TNF-a, IL-1b and IL-6 in murine neutrophils
Purification and characterization of a cold active alkaline protease from Stenotrophomonas sp., isolated from Kashmir, India
No full textA Psychrotolerant alkaline protease producing bacterium IIIM-ST045 was isolated from a soil sample collected from the Thajiwas glacier of Kashmir, India and identified as Stenotrophomonas sp. on the basis of its biochemical properties and 16S ribosomal gene sequencing. The strain could grow well within a temperature range of 4–37�C however, showed optimum growth at 15�C. The strain was found to over-produce proteases when it was grown in media containing lactose as carbon source (157.50 U mg-1). The maximum specific enzyme activity (398 U mg-1) was obtained using soya oil as nitrogen source, however, the inorganic nitrogen sources urea,ammonium chloride and ammonium sulphate showed the lowest production of 38.9, 62.2 and 57.9 U mg-1. The enzyme was purified to 18.45 folds and the molecular weight of the partially purified protease was estimated to be *55 kDa by SDS-PAGE analysis. The protease activity increased as the increase in enzyme concentration while as the optimum enzyme activity was found when casein (1% w/v) was used as substrate. The enzyme was highly active
over a wide range of pH from 6.5 to 12.0 showing optimum
activity at pH 10.0. The optimum temperature for the enzyme was 15�C. Proteolytic activity reduced gradually with higher temperatures with a decrease of 56% at 40�C.
The purified enzyme was checked for the removal of protein
containing tea stains using a silk cloth within a temperature range of 10–60�C. The best washing efficiency
results obtained at low temperatures indicate that the
enzyme may be used for cold washing purposes of delicate
fabrics that otherwise are vulnerable to high temperatures
Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus
No full textPiperine, a trans-trans-isomer of 1-piperoyl-piperidine, was tested in combination with mupirocin for antimicrobial activity against Staphylococcus aureus strains including meticillin-resistant S. aureus. The combination markedly reduced the MIC of mupirocin and also lowered the
mutation frequency. Enhanced accumulation and efflux of ethidium bromide from wild-type and mutant (Mupr-1) strains in the presence of piperine indicated that inhibition of efflux could be a possible mechanism of potentiation of mupirocin activity by piperine. The combination of piperine ; with mupirocin in a dermal infection model of mice showed better in vivo efficacy when compared with the commercially available formulation of 2% mupirocin
N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors
No full textA series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin–West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure–activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase
inhibitor (IC50 = 2.45 lM) as well as the most potent anti-hyperuricemic agent. The basis of significant
inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase
Highly Regio- and Stereoselective One-Pot Synthesis of Carbohydrate-Based Butyrolactones
No full textThe use of manganese(III) acetate allows the direct synthesis of diverse arrays of [4.3.0] bicyclic carbohydrate-based γ-lactone building blocks from glycals. A mechanism to explain the high regio- and stereoselectivity is proposed. The new reaction has the potential to generate libraries for
biological screening