ESTIMATION OF ALKALOIDS AND PHENOLICS OF FIVE EDIBLE CUCURBITACEOUS PLANTS AND THEIR ANTIBACTERIAL ACTIVITY

Objective: Objective of the present work was qualitative and quantitative estimation of alkaloids and phenolics of five edible cucurbitaceous plants and to evaluate their antibacterial activity against some human pathogenic bacteria.Methods: Total alkaloid present was determined by acid-based titrimetric methods using methyl red as an indicator and observing a faint yellow end point. Total phenolics were estimated by follin-ciocaltue's method using tannic acid as standard. Antibacterial activity was determined by Disc diffusion method using SRL Agar medium. The 70% ethanolic dried powdered was dissolved in 20% DMSO at different concentration to carry out the anti-microbial activity.Results: It was found that all the experimental plants contained almost equal amount of alkaloids but their phenolic contents as tannic acid equivalents were different. Alkaloids content of five Cucurbitaceous plants were found to vary from 1.15 g % to 1.34 g % and phenol content was varied from 4.54 mg/g to 10.13 mg/g. All the selected Cucurbitaceous plants were active against the tested pathogens, except against V. cholerae non.0139 (L4). Only the 70% ethanolic leaf extract of Momordica charantia (Linn.) showed a relative percentage inhibition from 15.02 to 16.63. So, Momordica charantia (Linn.) extract was the most active among five selected plants against the tested pathogens.Conclusion: The activity might be due to the presence of alkaloids and phenols. However, the extent of activity or zone of inhibition was found varied for different extracts might be due to the difference in the constituents present in the plant extracts

Preparation of rare earth oxide doped alumina ceramics, their hardness and fracture toughness determinations

443-450Alumina based ceramics doped with rare earth oxide (Y2O3) of 500 ppm, 1000 ppm and 2000 ppm were prepared by following ceramic powder processing and solid state sintering at 1500°C for different soaking time periods of 3 h, 6 h and 9 h. Microstructural investigations on all the samples were carried out. Hardness measurements were conducted using Vickers Indentation technique. Fracture toughness of the samples was estimated by inducing radial cracks by various indentation loads on the samples. The measured hardness values were found to lie between 139 MPa and 1444 MPa, while the fracture toughness values lie in the range 1.65-5.76 MPa m1/2</sup

Plasticity in [(R<SUB>4-x</SUB>R<SUP>1</SUP><SUB>x</SUB>)<SUB>4</SUB>N]<SUB>4</SUB>[Cu<SUB>4</SUB>{S<SUB>2</SUB>C<SUB>2</SUB >(CN)<SUB>2</SUB>}<SUB>4</SUB>] (x = 0-4) is molded by a guest cation on an elastic anionic host

The elastic anion [Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>]<SUP>4-</SUP> {mnt = maleonitriledithiolato, [S<SUB>2</SUB>C<SUB>2</SUB>(CN)<SUB>2</SUB>]<SUP>2-</SUP>} serves as a host to a series of guest cations [(R<SUB>4-x</SUB>R<SUP>1</SUP><SUB>x</SUB>)<SUB>4</SUB>N]<SUP>+</SUP> (R = Et, R<SUP>1</SUP> = Me; x = 0-4) to form the complexes [(R<SUB>4-x</SUB>R<SUP>1</SUP><SUB>x</SUB>)<SUB>4</SUB>N]<SUB>4</SUB>[Cu<SUB>4</SUB>{S<SUB>2</SUB>C<SUB>2</SUB >(CN)<SUB>2</SUB>}<SUB>4</SUB>]. The molecular structural design information stored in the cation is molded to the elastic anionic host-framework through H-bonding to create a plastic supramolecular entity. The reaction of CuCl with Na<SUB>2</SUB>(mnt) in a 1:1 metal/ligand ratio, followed by interaction with the respective cation, gives the cation-dependenttetranuclear host-guest assemblies [Me<SUB>4</SUB>N]<SUB>4</SUB>[Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>] (1), [Me<SUB>3</SUB>EtN]<SUB>4</SUB>[Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>] (2), [Me<SUB>2</SUB>Et<SUB>2</SUB>N]<SUB>4</SUB>[Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>] (3), [MeEt<SUB>3</SUB>N]<SUB>4</SUB>[Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>] (4) and [Et<SUB>4</SUB>N]<SUP>4</SUP>[Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>] (5), which have been characterized by X-ray structural studies in the solid state. The host cavity shrinks and expands, with varying Cu&#183;&#183;&#183;Cu separations ranging from 2.754 to 3.952 &#197;, to accommodate the relevant guest ion during the crystallization process. All these complexes show identical <SUP>13</SUP>C NMR and UV/Vis spectra in solution and their identical cyclic voltammetric redox behaviors also imply the presence of a common entity. The ESI mass spectra in acetonitrile confirm the presence of this common {Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>} core. The elastic {Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>} core participates in extensive hydrogen bonds in the presence of different quaternary cations in solution during the crystallization process and the cation determines the final shape of the anion in the solid state. Depending on the length and nature (symmetric or non-symmetric) of the alkyl groups attached to the quaternary cation, the overall geometry of the anion assumes different degrees of openness in a partially opened umbrella shape. The {Cu<SUB>4</SUB>(mnt)<SUB>4</SUB>} moiety is cleaved by treatment with PPh<SUB>3</SUB> to give a monomer, which has been isolated as [Et<SUB>4</SUB>N][Cu(mnt)PPh<SUB>3</SUB>] (6)

Flexible Cu<SUP>I</SUP>-thiolate clusters with relevance to metallothioneins

Simple Cu-thiolate chemistry was developed to demonstrate the presence of copper clusters with {Cu<SUB>4</SUB>S<SUB>6</SUB>}, {Cu<SUB>5</SUB>S<SUB>7</SUB>} and {Cu<SUB>6</SUB>S<SUB>4</SUB>} cores in relevance to copper-containing metallothioneins. The new hexanuclear tricoordinate triply bridging thiolatocopper(I) clusters [NEt<SUB>4</SUB>]<SUB>4</SUB>[Cu<SUB>6</SUB>(SPh)<SUB>4</SUB>Cl<SUB>6</SUB>] (1) and[NEt4]4[Cu6(SPh)4Br6] (2) were synthesized from the soup of polymeric [CuISPh]n and quaternary ammonium halide. These complexes readily converted into [Et<SUB>4</SUB>N]<SUB>2</SUB>[Cu<SUB>5</SUB>(SPh)<SUB>7</SUB>] (3) and [Et<SUB>4</SUB>N]<SUB>2</SUB>[Cu<SUB>4</SUB>(SPh)<SUB>6</SUB>] (4) in the presence of excess amounts of thiol. All are structurally characterized by single-crystal X-ray crystallography and these smaller clusters may be inscribed into the structurally characterized larger cluster {Cu<SUB>8</SUB>S10} obtained from synthetic copper yeast metallothioneins. Like Cu-MT proteins, all these clusters show photoluminescence around 560 nm on excitation at 350 nm, and these emission spectra are completely quenched by molecular oxygen. Variable copper stoichiometry and the interconversion of only monodentate thiolate ligands in these clusters convey the importance of flexibility, which is relevant to metallothioneins

Selective inclusion of DMF molecules within non-covalent cavity

[Me4P]4[Cu4(mnt)4]·2CH3CN (1), [Me4P]4[Cu4(mnt)4]·2CH3NO2 (2), [Me4P]4[Cu4(mnt)4]·2DMF (3) and [Me4P]4[Cu4(mnt)4]·2C3H3N (4) (mnt= maleonitriledithiolate, [S2C2(CN)2]2−) clusters are readily synthesized in several solvents like acetonitrile, nitromethane, N,N-dimethylformamide and acrylonitrile to provide respective solvent as guest within the non-covalent cavity of the cluster ion. The guest species is accommodated within non-covalent cavity that is generated by two adjacent {Cu4(mnt)4} cores bridging with tetramethylphosphonium cation through hydrogen bonding. These hydrogen bonds are not strong and when mixed solvents were used selective DMF binding takes place to yield only complex 3 over other complexes

Lipodox® (generic doxorubicin hydrochloride liposome injection): in vivo efficacy and bioequivalence versus Caelyx® (doxorubicin hydrochloride liposome injection) in human mammary carcinoma (MX-1) xenograft and syngeneic fibrosarcoma (WEHI 164) mouse models

Abstract Background Doxorubicin (DXR) hydrochloride (HCl) liposome injection is an important part of the treatment armamentarium for a number of cancers. With growing needs for affordable and effective anticancer treatments, the development of generics is becoming increasingly important to facilitate patient access to vital medications. We conducted studies in relevant mouse models of cancer to compare the preclinical antitumour efficacy and plasma pharmacokinetic profile of a proposed generic DXR HCl liposome injection developed by Sun Pharmaceutical Industries Ltd. (SPIL DXR HCl liposome injection) with Caelyx® (reference DXR HCl liposome injection). Methods Syngeneic fibrosarcoma (WEHI 164)-bearing BALB/c mice and athymic nude mice transplanted with MX-1 human mammary carcinoma xenografts were treated with SPIL DXR HCl liposome injection, reference DXR HCl liposome injection or placebo, to compare tumour volume, antitumour activity (percentage test/control [%T/C] ratio, tumour regression, and specific tumour growth delay) and toxicity (survival and weight changes) in response to treatment. The pharmacokinetic profile of the SPIL and reference product was also studied in syngeneic fibrosarcoma-bearing mice. Results Treatment with either SPIL or reference DXR HCl liposome injection resulted in significant reduction in tumour volume from baseline in both models at all doses tested. High antitumour activity (%T/C ≤ 10) was seen from Day 21 and Day 14 onwards in SPIL and reference DXR HCl liposome injection–treated syngeneic fibrosarcoma-bearing mice, respectively, at 9 mg/kg. Moderate antitumour activity (%T/C ≤ 20) was seen from Day 17 and Day 24 onwards in SPIL and reference DXR HCl liposome injection–treated MX-1-bearing mice, respectively, at 6 mg/kg. No significant differences in tumour volume and %T/C were observed between SPIL and reference DXR HCl liposome injection–treated groups at any dose (p ≥ 0.05). Toxicity profiles were considered to be generally comparable. Evaluation of test/reference (A/B) ratios and 90% confidence intervals (CIs) for peak serum concentration (Cmax) and area under the curve (AUC0-t, and AUC0-∞) demonstrated bioequivalence of SPIL and reference DXR HCl liposome injections. Conclusions Establishing similarity is of critical importance during the development of generic treatments. SPIL and reference DXR HCl liposome injections were shown to be comparable with regards to antitumour activity, toxicity and pharmacokinetics

Some Functional Properties of khambir, an Ethnic Fermented Cereal-Based Food of Western Himalayas

Traditional leavened wheat-based flat bread khambir is a staple food for the high-altitude people of the Western Himalayan region. The health promoting abilities of two types of khambir, yeast added khambir (YAK) and buttermilk added khambir (BAK), were evaluated. A group of microbes like yeast, mold, lactic acid bacteria (LAB), and Bifidobacterium sp. were abundant in both khambir but in varied proportions. Both are enriched with phenolics and flavonoids. The aqueous extracts of both breads strongly inhibited the growth of enteropathogens. Molecular docking experiments showed that phenolic acid, particularly p-coumaric acid, blocked the active sites of β-glucosidase and acetylcholine esterase (AChE), thereby inhibiting their activities. YAK and BAK showed antiradical and antioxidant activity ranging from 46 to 67% evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing/antioxidant power (FRAP) assays. The aqueous extract of both khambir samples protected the arsenic toxicity when examined under an in situ rat intestinal loop model study. The arsenic induced elevated levels of superoxide dismutase (SOD), catalase (CAT), reduced glutathione, lipid peroxidation (LPO) and DNA fragmentation, and transmembrane mitochondrial potential was alleviated by khambir extract. These results scientifically supported its age-old health benefit claims by the consumer at high altitude and there are enough potentialities to explore khambir as a medicinal food for human welfare

One Electron Reduced Square Planar Bis(benzene-1,2-dithiolato) Copper Dianionic Complex and Redox Switch by O2/HO−

The complex [Ph4P]2[Cu(bdt)2] (1red) was synthesized by the reaction of [Ph4P]2[S2MoS2CuCl] with H2bdt (bdt = benzene-1,2-dithiolate) in basic medium. 1red is highly susceptible toward dioxygen, affording the one electron oxidized diamagnetic compound [Ph4P][Cu(bdt)2] (1ox). The interconversion between these two oxidation states can be switched by addition of O2 or base (Et4NOH = tetraethylammonium hydroxide), as demonstrated by cyclic voltammetry and UV–visible and EPR spectroscopies. Thiomolybdates, in free or complex forms with copper ions, play an important role in the stability of 1red during its synthesis, since in its absence, 1ox is isolated. Both 1red and 1ox were structurally characterized by X-ray crystallography. EPR experiments showed that 1red is a Cu(II)–sulfur complex and revealed strong covalency on the copper–sulfur bonds. DFT calculations confirmed the spin density delocalization over the four sulfur atoms (76%) and copper (24%) atom, suggesting that 1red has a “thiyl radical character”. Time dependent DFT calculations identified such ligand to ligand charge transfer transitions. Accordingly, 1red is better described by the two isoelectronic structures [CuI(bdt2, 4S3–,*)]2– ↔ [CuII(bdt2, 4S4–)]2–. On thermodynamic grounds, oxidation of 1red (doublet state) leads to 1ox singlet state, [CuIII(bdt2, 4S4–)]1–.Fil: Maiti, Biplab K.. Universidade Nova de Lisboa; PortugalFil: Maia, Luisa B.. Universidade Nova de Lisboa; PortugalFil: Pal, Kuntal. University of Manchester; Reino UnidoFil: Pakhira, Bholanath. Indian Institute of Engineering Science and Technology; IndiaFil: Avilés,Teresa. Universidade Nova de Lisboa; PortugalFil: Moura, Isabel. Universidade Nova de Lisboa; PortugalFil: Pauleta, Sofia R.. Universidade Nova de Lisboa; PortugalFil: Nuñez, José L.. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; ArgentinaFil: Rizzi, Alberto Claudio. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Brondino, Carlos Dante. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; ArgentinaFil: Sarkar, Sabyasachi. Indian Institute of Engineering Science and Technology; IndiaFil: Moura, José J. G.. Universidade Nova de Lisboa; Portuga