Synthesis, crystal structures, DNA binding and cleavage activity of L-glutamine copper(II) complexes of heterocyclic bases

Ternary L-glutamine (L-gln) copper(II) complexes [Cu(L-gln)(B)(H2O)](X) (B = 2,2'-bipyridine (bpy), X = 0.5SO(4)(2-), 1; B = 1,10-phenanthroline (phen), X = ClO4-, 2) and [Cu(L-gln)(dpq)(ClO4)] (3) (dpq, dipyridoquinoxaline) are prepared and characterized by physicochemical methods. The DNA binding and cleavage activity of the complexes have been studied. Complexes 1-3 are structurally characterized by X-ray crystallography. The complexes show distorted square pyramidal (4+1) CuN3O2 coordination geometry in which the N,O-donor amino acid and the N, N-donor heterocyclic base bind at the basal plane with a H2O or perchlorate as the axial ligand. The crystal structures of the complexes exhibit chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The complexes display a d-d electronic band in the range of 610-630 nm in aqueous-dimethylformamide (DMF) solution (9:1 v/v). The quasireversible cyclic voltammetric response observed near -0.1 V versus SCE in DMF-TBAP is assignable to the Cu(II)/Cu(I) couple. The binding affinity of the complexes to calf thymus (CT) DNA follows the order: 3 (dpq) > 2 (phen) >> 1 (bpy). Complexes 2 and 3 show DNA cleavage activity in dark in the presence of 3-mercaptopropionic acid (MPA) as a reducing agent via a mechanistic pathway forming hydroxyl radical as the reactive species. The dpq complex 3 shows efficient photoinduced DNA cleavage activity on irradiation with a monochromatic UV light of 365 nm in absence of any external reagent. The cleavage efficiency of the DNA minor groove binding complexes follows the order:3 > 2 >> 1. The dpq complex exhibits photocleavage of DNA on irradiation with visible light of 647.1 nm. Mechanistic data on the photo-induced DNA cleavage reactions reveal the involvement of singlet oxygen (O-1(2)) as the reactive species in a type-II pathway. (C) 2008 Elsevier B.V. All rights reserved.

Synthesis, crystal structures and protease activity of amino acid Schiff base iron(III) complexes

Iron(III) complexes, (NHEt3)[Fe(III)(sal-met)(2)] and (NHEt3)[Fe(III)(sal-phe)(2)], of amino acid Schiffbase ligands, viz., N-salicylidene-L-methionine and N-salicylidene L-phenylalanine, have been prepared and their binding to bovine serum albumin (BSA) and photo-induced BSA cleavage activity have been investigated. The complexes are structurally characterized by single crystal X-ray crystallography. The crystal Structures of the discrete mononuclear rnonoanionic complexes show FeN2O4 octahedral coordination geometry in which the tridentate dianionic amino acid Schiff base ligand binds through phenolate and carboxylate oxygen and imine nitrogen atoms. The imine nitrogen atoms are trans to each other. The Fe-O and Fe-N bond distances range between 1.9 and 2.1 angstrom. The sal-met complex has two pendant thiomethyl groups. The high-spin iron(III) complexes (mu(eff) similar to 5.9 mu(B)) exhibit quasi-reversible Fe(III)/Fe(II) redox process near -0.6 V vs. SCE in water. These complexes display a visible electronic hand near 480 nm in tris-HCl buffer assignable to the phenolate-to-iron(III) charge transfer transition. The water soluble complexes bind to BSA giving binding constant values of similar to 10(5) M-1. The Complexes show non-specific oxidative cleavage of BSA protein on photo-irradiation with UV-A light of 365 nm.

Synthesis, characterization and photocatalytic activity of MxCe1-xVO4 (M = Li, Ca and Fe)

Non-stoichiometric substituted cerium vanadates, MxCe1-xVO4 (M = Li, Ca and Fe), were synthesized by solid-state reactions. The crystal structure was analyzed by powder X-ray diffraction and it exhibits a tetragonal zircon Structure, crystallizing in the space group I4(1)/amd with a = 7.3733(4) and c = 6.4909(4) angstrom and Z = 4. Particle sizes were in the range of 600-800 nm, as observed by scanning electron microscopy. The thermal analysis of the compounds showed phase stability up to 1100 degrees C. The UV diffuse reflectance spectra indicated that the compounds have band gaps in the range of 2.6-2.9 eV. The photocatalytic activity of these Compounds was investigated for the first time for the degradation of different dyes, and organics, the oxidation of cyclohexane and the hydroxylation of benzene. The degradation of dyes was modeled using the Langmuir-Hinshelwood kinetics, while the oxidation of cyclohexane and hydroxylation of benzene were modeled using a free radical mechanism and a series reaction mechanism, respectively.

Theoretical studies on Beta-lactam antibiotics VI: Conformational analysis and structure-activity relationships of penicillin sulfoxides and cephalosporins

Conformational energy calculations were carried out on penicillin α-and Β-sulfoxides and δ2- and δ3-cephalosporins, in order to identify the structural features governing their biological activity. Results on penicillin Β-sulfoxide indicated that in its favoured conformation, the orientation of the aminoacyl group was different from the one required for biological activity. Penicillin α sulfoxide, like penicillin sulfide, favoured two conformations of nearly equal energies, but separated by a much higher energy barrier. The reduced activity of the sulfoxides despite the nonplanarity of their lactam peptide indicated that the orientations of the aminoacyl and carboxyl groups might also govern biological activity. δ3-cephalosporins favoured two conformations of nearly equal energies, whereas δ2-cephalosporins favoured only one conformation. The lactam peptide was moderately nonplanÄr in the former, but nearly planar in the latter. The differences in the.preferred orientations of the carboxyl group between penicillins and cephalosporins were correlated with the resistance of cephalosporins to penicillinases.

Synthesis and Structure-Activity Correlation Studies of Secondary- and Tertiary-Amine-Based Glutathione Peroxidase Mimics

In this study, a series of seeondary- and tertiary-amino-substituted diaryl diselenides were synthesized and studied for their glutathione peroxidase (GPx) like antioxidant activities with H2O2, cumene hydroperoxide, or tBuOOH as substrates and with PhSH or glutathione (GSH) as thiol cosubstrates. This study reveals that replacement of the tert-amino groups in benzylamine-based diselenides by sec-amino moieties drastically enhances the catalytic activities in both the aromatic thiol (PhSH) and GSH assay systems. Particularly, the N-propyl- and N-isopropylamino-substituted diselenides are 8-18 times more active than the corresponding N,N-dipropyl- and N,N-diisopropylamine-based compounds in all three peroxide systems when GSH is used as the thiol cosubstrate. Although the catalytic mechanism of sec-amino-substituted disclenides is similar to that of the tert-amine-based compounds, differences in the stability and reactivity of some of the key intermediates account for the differences in the GPx-like activities. it is observed that the sec-amino groups are better than the tert-amino moieties for generating the catalytically active selenols. This is due to the absence of any significant thiol-exchange reactions in the selenenyl sulfides derived from sec-amine-based diselenides. Furthermore, the seleninic acids (RSeO2H) derived from the sec-amine-based compounds are more stable toward further reactions with peroxides than their tert-amine-based analogues.

The influence of esterification of carboxyl groups of ribonuclease-a on its structure and immunological activity

The effect of modification of carboxyl groups of Ribonuclease-Aa on the enzymatic activity and the antigenic structure of the protein has been studied. Modification of four of the eleven free carboxyl groups of the protein by esterification in anhydrous methanol/0.1 M hydrochloric acid resulted in nearly 80% loss in enzymatic activity but had very little influence on the antigenic structure of the protein. Further increases in the modification of the carboxyl groups caused a progressive loss in immunological activity, and the fully methylated RNase-A exhibited nearly 30% immunological activity. Concomitant with this change in the antigenic structure of the protein, the ability of the molecule to complement with RNase-S-protein increased, clearly indicating the unfolding of the peptide "tail" from the remainder of the molecule. The susceptibility to proteolysis, accessibility of methionine residues for orthobenzoquinone reaction and the loss in immunological activity of the more extensively esterified derivatives of RNase-A are suggestive of the more flexible conformation of these derivatives as compared with the compact native conformation. The fact that even the fully methylated RNase-A retains nearly 30% of its immunological activity suggested that the modified protein contained antibody recognizable residual native structure, which presumably accommodates some antigenic determinants.

Iron(III) Schiff base complexes of arginine and lysine as netropsin mimics showing AT-selective DNA binding and photonuclease activity

Iron(III) complexes [Fe(L)(2)]Cl (1-3), where L is monoanionic N-salicylidene-arginine (sal-argH for 1), hydroxynaphthylidene-arginine (nap-argH for 2) and N-salicylidene-lysine (sal-lysH for 3), were prepared and their DNA binding and photo-induced DNA cleavage activity studied. Complex 3 as its hexafluorophosphate salt [Fe(sal-lysH)(2)](PF6)center dot 6H(2)O (3a) was structurally characterized by single crystal Xray crystallography. The crystals belonged to the triclinic space group P-1. The complex has two tridentate ligands in FeN2O4 coordination geometry with two pendant cationic amine moieties. Complexes 1 and 2 with two pendant cationic guanidinium moieties are the structural models for the antitumor antibiotics netropsin. The complexes are stable and soluble in water. They showed quasi-reversible Fe(III)/Fe(II) redox couple near 0.6 V in H2O-0.1 M KCl. The high-spin 3d(5)-iron(III) complexes with mu(eff) value of similar to 5.9 mu(B) displayed ligand-to-metal charge transfer electronic band near 500 mm in Tris-HCl buffer. The complexes show binding to Calf Thymus (CT) DNA. Complex 2 showed better binding propensity to the synthetic oligomer poly(dA)center dot poly(dT) than to CT-DNA or poly(dG)center dot poly(dC). All the complexes displayed chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent and cleaved supercoiled pUC19 DNA to its nicked circular form. They exhibited photo-induced DNA cleavage activity in UV-A light and visible light via a mechanistic pathway that involves the formation of reactive hydroxyl radical species. (C) 2010 Elsevier Inc. All rights reserved.

Synthesis and Antileukemic Activity of 1-((S)-2-Amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea Derivatives

Heterocyclic urea derivatives play an important role as anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis. Benzothiazole moiety constitutes an important scaffold of drugs, possessing several pharmacological functions, mainly the anticancer activity. Based on these interesting properties of benzothiazoles and urea moiety to obtain new biologically active agents, we synthesized a series of novel 1-((S)-2-amino-4,5,6.7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea derivatives and evaluated for their efficacy as antileukemic agents against two human leukemic cell lines (K562 and Reh). These compounds showed good and moderate cytotoxic effect to cancer cell lines tested. Compounds with electron-withdrawing chloro and fluoro substituents on phenyl ring showed good activity and compounds with electron-donating methoxy group showed moderate activity. Compound with electron-withdrawing dichloro substitution on phenyl ring of aryl urea showed good activity. Further, lactate dehydrogenase (LDH) assay, flow cytometric analysis of annexin V-FITC/propidium iodide (PI) double staining and DNA fragmentation studies showed that compound with dichloro substitution on phenyl ring of aryl urea can induce apoptosis.

Growth of and trehalase activity in the thermophilic fungusThermomyces lanuginosus

The thermophilic fungus,Thermomyces lanuginosus, was grown in a glucose-asparagine liquid medium. Optimal mycelial growth occurred at 50°C. The conditions for sporulation were different from those required for vegetative growth. the former being favoured by lower nitrogen level and temperature. Trehalase (α, α-glu coside-l-glucohydrolase, EC 3.2.1.28) was one of the most active glycosidases at 50°C. Non-sporulating mycelium had higher levels of this enzyme than the sporulating mycelium. Trehalase was synthesized constitutively and its activity appears to be controlled by catabolite repression.

Ferrocene-Promoted Photoactivated DNA Cleavage and Anticancer Activity of Terpyridyl Copper(II) Phenanthroline Complexes

Ferrocene-appended copper(II) complexes [Cu( Fc-tpy)(B)](ClO4)(2) (1-3) and [Cu(Ph-tpy)(dppz)](ClO4)(2) (4) as control, where Fc-tpy is 4'-ferroceny1-2,2':6',2 ''-terpyridine, Ph-tpy is 4'-pheny1-2,2':6',2 ''-terpyridine, and B is a phenanthroline base, viz., 1,10-phenanthroline (phen, 1), dipyridoquinoxaline (dpq, 2), and dipyridophenazine (dppz, 3), were prepared and structurally characterized, and their DNA binding, photoactivated DNA cleavage activity, and cytotoxic properties were studied [Fe = (eta(5)-C5H4)Fe-11(eta(5)-C5H5)]. Complexes 1 and 3 as hexafluorophosphate salts were structurally characterized by X-ray crystallography. Molecular structures of [Cu(Fc-tpy)(phen)](PF6)(2) (1a) and [Cu(Fc-tpy)(dppz)](PF6)(2)center dot MeCN (3a center dot MeCN) show a distorted square-pyramidal geometry at copper(II), with the Fc-tpy ligand and the phenanthroline base showing respective tridentate and bidentate binding modes. The phenanthroline base exhibits axial-equatorial bonding, while the Fc-tpy ligand binds at the basal plane. The complexes showed quasi-reversible cyclic voltammetric responses near 0.45 and -0.3 V vs SCE in aqueous DMF-0.1 M KCl assignable to the Fc(+)-Fc and Cu(II) Cu(1) redox couples, respectively. The complexes bind to DNA, giving K-b values of 1.4 x 10(4) to 5.6 x 10(5) M-1 in the order 4 similar to 3 > 2 > 1. Thermal denaturation and viscometric titration data suggest groove and/or partial intercalative mode of DNA binding of the complexes. The complexes showed chemical nuclease activity in the presence of 3-mercaptopropionic acid (0.5 mM) or H2O2 (0.25 mM). Complexes 2-4 showed plasmid DNA cleavage activity in visible light, forming (OH)-O-center dot radicals. The Fc-tpy complex 3 showed better DNA photocleavage activity than its Ph-tpy analogue. The ferrocene moiety in the dppz complex 3 makes it more photocytotoxic than the Ph-tpy analogue 4 in HeLa cells.

Differential regulation of MRN (Mre11-Rad50-Nbs1) complex subunits and telomerase activity in cancer cells

Several lines of evidence suggest that cancer progression is associated with up-regulation or reactivation of telomerase and the underlying mechanism remains an active area of research. The heterotrimeric MRN complex, consisting of Mre11, Rad50 and Nbs1, which is required for the repair of double-strand breaks, plays a key role in telomere length maintenance. In this study, we show significant differences in the levels of expression of MRN complex subunits among various cancer cells and somatic cells. Notably, siRNA-mediated depletion of any of the subunits of MRN complex led to complete ablation of other subunits of the complex. Treatment of leukemia and prostate cancer cells with etoposide lead to increased expression of MRN complex subunits, with concomitant decrease in the levels of telomerase activity, compared to breast cancer cells. These studies raise the possibility of developing anti-cancer drugs targeting MRN complex subunits to sensitize a subset of cancer cells to radio- and/or chemotherapy. (C) 2010 Elsevier Inc. All rights reserved.

DNA photocleavage and anticancer activity of terpyridine copper(II) complexes having phenanthroline bases

Copper(II) complexes Cu(ph-tpy)(B)](ClO4) (1-3), where ph-tpy is (4'-phenyl)-2,2':6',2 `'-terpyridine and B is N,N-donor phenanthroline base, viz. 1,10-phenanthroline (phen, 1), dipyridoquinoxaline (dpq, 2), and dipyridophenazine (dppz, 3), were prepared and characterized from analytical and spectral data. Complex 1, characterized by X-ray crystallography, shows a distorted square-pyramidal (4 + 1) CuN5 coordination geometry having the tridentate ph-tpy ligand at the basal plane and bidentate phen bound to the axial-equatorial sites. The complexes display a d-d band near 650 nm in aqueous DMF. The complexes are avid binders to calf thymus DNA giving the binding order: 3 (dppz) > 2 (dpq) > 1 (phen). The dpq and dppz complexes show photo-induced DNA cleavage activity in red light via photo-redox pathway forming hydroxyl radicals. The cytotoxicity of the dppz complex 3 was studied by MTT assay in HeLa cancer cells. The IC50 values are 3.7 and 12.4 mu M in visible light of 400-700 nm and dark, respectively. (C) 2010 Elsevier Ltd. All rights reserved.

Antipyretic and antibacterial activity of Chloranthus erectus (Buch.-Ham.) Verdcourt leaf extract: A popular folk medicine of Arunachal Pradesh

Objective : The main objective of this work was to study the antipyretic and antibacterial activity of C. erectus (Buch.-Ham.) Verdcourt leaf extract in an experimental albino rat model. Materials and Methods : The methanol extract of C. erectus leaf (MECEL) was evaluated for its antipyretic potential on normal body temperature and Brewers yeast-induced pyrexia in albino rats model. While the antibacterial activity of MECEL against five Gram (-) and three Gram () bacterial strains and antimycotic activity was investigated against four fungi using agar disk diffusion and microdilution methods. Result : Yeast suspension (10 mL/kg b.w.) elevated rectal temperature after 19 h of subcutaneous injection. Oral administration of MECEL at 100 and 200 mg/kg b.w. showed significant reduction of normal rectal body temperature and yeast-provoked elevated temperature (38.8 0.2 and 37.6 0.4, respectively, at 2-3 h) in a dose-dependent manner, and the effect was comparable to that of the standard antipyretic drug-paracetamol (150 mg/kg b.w.). MECEL at 2 mg/disk showed broad spectrum of growth inhibition activity against both groups of bacteria. However, MECEL was not effective against the yeast strains tested in this study. Conclusion : This study revealed that the methanol extract of C. erectus exhibited significant antipyretic activity in the tested models and antibacterial activity as well, and may provide the scientific rationale for its popular use as antipyretic agent in Khamptiss folk medicines.

Highly dispersed ultrafine Pt and PtRu nanoparticles on graphene: formation mechanism and electrocatalytic activity

We demonstrate a robust strategy for obtaining a high dispersion of ultrafine Pt and PtRu nanoparticles on graphene by exploiting the nucleation of a metal precursor phase on graphite oxide surfaces. Our method opens up new possibilities to engineer graphene-based hybrids for applications in multifunctional nanoscale devices.