Synthesis and identification of a new class of (S)-2,6-diamino-4,5,6,7-tetrahydrobenzo[d]thiazole derivatives as potent antileukemic agents

Benzothiazoles are multitarget agents with broad spectrum of biological activity. Among the antitumor agents discovered in recent years, the identification of various 2-(4-aminophenyl) benzothiazoles as potent and selective antitumor drugs against different cancer cell lines has stimulated remarkable interest. Some of the benzothiazoles are known to induce cell cycle arrest, activation of caspases and interaction with DNA molecule. Based on these interesting properties of benzothiazoles and to obtain new biologically active agents, a series of novel 4,5,6,7-tetrahydrobenzo[d]thiazole derivatives 5(a-i) were synthesized and evaluated for their efficacy as antileukemic agents in human leukemia cells (K562 and Reh). The chemical structures of the synthesized compounds were confirmed by H-1 NMR, LCMS and IR analysis. The cytotoxicity of these compounds were determined using trypan blue exclusion, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results showed that, these compounds mediate a significant cytotoxic response to cancer cell lines tested. We found that the compounds having electron withdrawing groups at different positions of the phenyl ring of the thiourea moiety displayed significant cytotoxic effect with IC50 value less than 60 mu M. To rationalize the role of electron withdrawing group in the induction of cytotoxicity, we have chosen molecule 5g (IC50 similar to 15 mu M) which is having chloro substitution at ortho and para positions. Flow cytometric analysis of annexin V-FITC/ propidium iodide (PI) double staining and DNA fragmentation suggest that 5g can induce apoptosis.

Group fission in Nilgiri langurs (Presbytis johnii)

During a field study on habituated groups of wild Nilgiri langurs (Presbytis johnii), four cases of group fission were observed which differed markedly from group changes reported in other species of the same genus. All fissions occurred in groups with more than one mature male and roughly coincided with the onset of loud call vocalization by the second mature male group member. As a result of the fission the founder group factions acquired the structure of a onemale group. The filial factions consisted of both mature males and females and occupied, at least temporarily, a part of, or an area adjacent to, the founder group. During fission, the amount of aggressive interactions between the two mature males increased. However, the majority of agonistic interactions involved ritualized threat and intimidation behavior without physical aggression. In at least three cases the two mature males involved in the fission had not joined recently but had lived in these groups for three years or more. Although the presence of all male bands and single males in the two study populations indicate that male replacement by invasive takeovers may occur, it is suggested that in Nilgiri langurs, noninvasive fissions are probably another common mechanism for the foundation and maintenance of bisexual one-male groups.

Nanomechanical Characterization of Indium Nano/Microwires

Nanomechanical properties of indium nanowires like structures fabricated on quartz substrate by trench template technique, measured using nanoindentation. The hardness and elastic modulus of wires were measured and compared with the values of indium thin film. Displacementburst observed while indenting the nanowire. `Wire-only hardness' obtained using Korsunsky model from composite hardness. Nanowires have exhibited almost same modulus as indium thin film but considerable changes were observed in hardness value.

Photocytotoxicity and DNA cleavage activity of L-arg and L-lys Schiff base oxovanadium(IV) complexes having phenanthroline bases

Oxovanadium(IV) complexes [VO(sal-argH)(B)] Cl (1-3) and [VO(sal-lysH)(B)] Cl (4-6), where sal-argH2 and sal-lysH(2) are N-salicylidene-L-arginine and N-salicylidene-L-lysine Schiff bases and B is a phenanthroline base, viz. 1,10-phenanthroline (phen in 1 and 4); dipyrido[3,2-d: 2', 3'-f] quinoxaline (dpq in 2 and 5) and dipyrido[3,2-a: 2', 3'-c] phenazine (dppz in 3 and 6), have been prepared, characterized and their DNA photocleavage activity studied. Complex 1, characterized by X-ray crystallography, shows the presence of a vanadyl group in VIVO3N3 coordination geometry with a tridentate Schiff base having a pendant guanidinium moiety and bidentate phen ligand. The complexes exhibit a d-d band at similar to 715 nm in 20% DMF-Tris-HCl buffer. The complexes are redox active showing cathodic and anodic responses near -1.0 V and 0.85 V (vs. SCE) for the V(IV)-V(III) and V(V)-V(IV) couples, respectively, in DMF-Tris-HCl buffer. The complexes bind to calf thymus DNA giving Kb values in the range of 3.8 x 10(4) to 1.6 x 10(5) M-1. Thermal denaturation and viscosity data suggest DNA groove binding nature of the complexes. The complexes do not show any `chemical nuclease'' activity in dark in the presence of 3-mercaptopropionic acid or H2O2. The dpq and dppz complexes are efficient photocleavers of plasmid DNA in UV-A (365 nm) and red light (676 nm) via singlet oxygen pathway. The dppz complexes exhibit photocytotoxicity in HeLa cancer cells giving IC50 values of 15.4 mu M for 3 and 17.5 mu M for 6 in visible light while being non-toxic in dark giving IC50 values of > 100 mu M.

Surface Structures of Silicon and Germanium

Si and Ge were cleaved on the (111) plane under ultra high vacuum and exposed to O and subsequent heat treatment. LEED and spot photometric measurements were taken. Cleaved surfaces for both Si and Ge gave the expected (2 x 1) structure. Results for O exposure were qualitatively for Si and Ge. The 1/2 orders disappeared after exposure to approx = 10 exp - exp 7. Integral orders started to weaken at 10 exp -6 to 10 exp - exp 2 torr min., disappearing at 10 exp -1 torr min. Heat treatment of Si at 900 deg C for several seconds restored the integral orders and further heating gave a new pattern with 1/3 orders. Exposure to 2 x 10 exp -6 torr min O without further heating weakened the fractional orders and at 10 exp -5 torr min they disappeared. Integral orders remained after further heating in O. For Ge integral orders were not restored after 0 exposure until heat treatment had continued at 550 deg C for several min. The (1 x 1) structure disappeared after heating at 590 deg C in 7 x 10 exp -1 torr O and further heating at 590 deg C without O restored the integral order Variations of intensity with voltage were measured for the (00) and (20) spots. The results supported a model proposed by Haneman (Phys. Rev., 1968, 170, 705) involving two kinds of atom sites on the cleaved surface. 20 ref.--E.J.S.

Giant planar Hall effect in pulsed laser deposited permalloy films

Ni80Fe20 thin films with high orientation were grown on Si(1 0 0) using pulsed laser ablation. The anisotropic magnetoresistance (AMR) and the planar Hall measurements show a 2.5% resistance anisotropy and a 45% planar Hall voltage change for magnetic field sweep of 10 Oe. The planar Hall sensitivity dR/dH was found to be 900 Omega T-1 compared with a previously reported maximum of 340 Omega T-1 in the same system.Also these films are found to withstand repeated thermal cycling up to 110 degrees C and the Hall sensitivity remains constant within this temperature range. This combination of properties makes the system highly suitable for low magnetic field sensors, particularly in geomagnetic and biosensor applications. To elucidate this, we have demonstrated that these sensors are sensitive to Earth's magnetic field. These results are compared with the sputter deposited films which have a very low AMR and planar Hall voltage change as compared with the films grown by PLD. The possible reasons for these contrasting characteristics are also discussed.

In vitro meristem cloning of Eucalyptus tereticornis Sm

Rapid multiplication of axillary meristems and direct shoot development occurred from nodal explants of mature Eucalyptus tereticornis Sm. with 5.3 mgrM NAA, 1.1 mgrM IAA and 4.4 mgrM BA in Murashige-Skoog medium. Repeated subcultures of the second generation shoot cultures into low cytokinin-auxin containing media (0.44�0.88 mgrM BA+0.1 mgrM NAA) yielded axillary microshoots in large numbers. Half-strength MS liquid medium with 4.9 mgrM IBA, 5.5 mgrM IAA and 5.3 mgrM NAA for four days, half-strength semi-solid hormonefree MS medium with charcoal, and MS liquid medium without charcoal and hormones, in sequence, induced rooting of shoots in the dark. This system is suitable for the mass propagation of this difficult-to-root eucalypt.

Anger is associated with subclinical atherosclerosis in low SES but not in higher SES men and women

We investigated the associations of anger and cynicism with carotid artery intima-media thickness (IMT) and whether these associations were moderated by childhood or adulthood socioeconomic status (SES). The participants were 647 men and 893 women derived from the population-based Cardiovascular Risk in Young Finns Study. Childhood SES was measured in 1980 when the participants were aged 3-18. In 2001, adulthood SES, anger, cynicism, and IMT were measured. There were no associations between anger or cynicism and IMT in the entire population, but anger was associated with thicker IMT in participants who had experienced low SES in childhood. This association persisted after adjustment for a host of cardiovascular risk factors. It is concluded that the ill health-effects of psychological factors such as anger may be more pronounced in individuals who have been exposed to adverse socioeconomic circumstances early in life.

Diproline Templates as Folding Nuclei in Designed Peptides. Conformational Analysis of Synthetic Peptide Helices Containing Amino Terminal Pro-Pro Segments

The effect of N-terminal diproline segments in nucleating helical folding in designed peptides has been studied in two model sequences Piv-Pro-Pro-Aib-Leu-Aib-Phe-OMe (1) and Boc-Aib-Pro-Pro-Aib-Val-Ala-Phe-OMe (2). The structure of 1 in crystals, determined by X-ray diffraction, reveals a helical (RR) conformation for the segment residues 2 to 5, stabilized by one 4 -> 1 hydrogen bond and two 5 -> 1 interactions. The N-terminus residue, Pro(1) adopts a polyproline II (P-II) conformation. NMR studies in three different solvent systems support a conformation similar to that observed in crystals. In the apolar solvent CDCl3, NOE data favor the population of both completely helical and partially unfolded structures. In the former, the Pro-Pro segment adopts an alpha(R)-alpha(R) conformation, whereas in the latter, a P-II-alpha(R) structure is established. The conformational equilibrium shifts in favor of the P-II-alpha(R) structure in solvents like methanol and DMSO. A significant population of the Pro(1)- Pro(2) cis conformer is also observed. The NMR results are consistent with the population of at least three conformational states about Pro- Pro segment: trans alpha(R)-alpha(R), trans P-II-alpha(R) and cis P-II-alpha(R). Of these, the two trans conformers are in rapid dynamic exchange on the NMR time scale, whereas the interconversion between cis and trans form is slow. Similar results are obtained with peptide 2. Analysis of 462 diproline segments in protein crystal structures reveals 25 examples of the alpha(R)-alpha(R) conformation followed by a helix. Modeling and energy minimization studies suggest that both P-II-alpha(R) and alpha(R)-alpha(R) conformations have very similar energies in the model hexapeptide 1

Radical cyclization strategies to terpenoids; syntheses of (±)-β-cuparenone, (±)-laurene and epilaurenes

Radical cyclization of the bromide Image , obtained in 5 steps from the ketone Image , furnished exclusively Image Image 6-endo trig cyclization with out any observable amount of 5-exo trig product Image . 5-Exo dig radical cyclizatlon of the bromo acetate Image , prepared from Image Image the aldehyde Image , followed by routine transformations furnished the cyclopentenone Image , an immediate precursor to β-cuparenone (Image ). Similarly, total synthesis of laurenes Image and Image was achieved Image the 5-exo dig radical cyclization of the xanthate Image , obtained from the aldehyde Image .Syntheses to title compounds based on 5-exo-dig radical cyclisation, along with two unsuccessful approaches to cuparene, are described.

Remark on factorials that are products of factorials

In a paper published in 1993, Erdos proved that if n! = a! b!, where 1 < a a parts per thousand currency sign b, then the difference between n and b does not exceed 5 log log n for large enough n. In the present paper, we improve this upper bound to ((1 + epsilon)/ log 2) log log n and generalize it to the equation a (1)!a (2)! ... a (k) ! = n!. In a recent paper, F. Luca proved that n - b = 1 for large enough n provided that the ABC-hypothesis holds.

X-ray studies on crystalline complexes involving amino acids and peptides. XXV. Structures of DL-proline hemisuccinic acid and glycyl-L-histidinium semisuccinate monohydrate and a comparative study of amino-acid and peptide complexes of succinic acid

DL-Proline hemisuccinic acid, C5H9NO2.1/2C4H6O4, M(r) = 174.2, P2(1/c) a = 5.254 (1), b = 17.480 (1), c = 10.230 (i) angstrom, beta = 119.60 (6)-degrees Z = 4, D(m) = 1.41 (4), D(x) = 1.42 g cm-3, R = 0.045 for 973 observed reflections. Glycyl-L-histidinium semisuccinate monohydrate, C8H13N4O3+.C4H5O4-.H2O, M(r) = 348.4, P2(1), a = 4.864 (1), b = 17.071 (2), c = 9.397 (1) angstrom, beta = 90.58-degrees, Z = 2, D(m) = 1.45 (1), D(x) = 1.48 g cm-3, R = 0.027 for 1610 observed reflections. Normal amino-acid and dipeptide aggregation patterns are preserved in the structures in spite of the presence of succinic acid/semisuccinate ions. In both the structures, the amino-acid/dipeptide layers stack in such a way that the succinic acid molecules/semisuccinate ions are enclosed in voids created during stacking. Substantial variability in the ionization state and the stoichiometry is observed in amino-acid and peptide complexes of succinic acid. Succinic acid molecules and succinate ions appear to prefer a planar centro-symmetric conformation with the two carboxyl (carboxylate) groups trans with respect to the central C=C bond. Considerable variation is seen in the departure from and modification of normal amino-acid aggregation patterns produced by the presence of succinic acid. Some of the complexes can be described as inclusion compounds with the amino acid/dipeptide as the 'host' and succinic acid/semisuccinate/succinate as the 'guest'. The effects of change in chirality, though very substantial, are not the same in different pairs of complexes involving DL and L isomers of the same amino acid.

Charge Transfer Complexes of Crown Ethers with 2, 3, 5, 6 - Tetracyano Pyrazine

The interaction of five crown ethers, 15-crown-5, 18-crown-6, benzo-15-crown-5, dibenzo-l8-crown-6, and dibenzo-24-crown-8 with 2, 3, 5, 6 - tetracyano pyrazine has been studied by spectroscopic methods. The association constants and thermodynamic parameters of the 1:1 complexes formed by donor ethers with the acceptor have been evaluated. There is an indication that oxygens of the ethers and aryl part of the ether act cooperatively in binding of the acceptor.

Crystal Structure of Sodium Deoxyinosine Monophosphate

The crystal and molecular structure of sodium deoxyinosine monophosphate (5'-dIMP) has been determined by x-ray crystallographic methods. The crystals belong to orthorhombic space group P212121, with a = 21.079(5) Aring, b = 9.206(3) Aring and c = 12.770(6) Aring. This deoxynucleotide shows common nucleotide features namely anti conformation about the glycosyl bond, C2' endo pucker for the deoxyribose sugar and gauche-gauche orientation for the phosphate group. The sodium ion is directly coordinated to the O3' atom, a feature observed in many crystal structures of sodium salts of nucleotides.

Dopamine receptors in human foetal brains:Characterization, regulation and ontogeny of [3H]spiperone binding sites in striatum

Eighteen corpora striata from normal human foetal brains ranging in gestational age from 16 to 40 weeks and five from post natal brains ranging from 23 days to 42 years were analysed for the ontogeny of dopamine receptors using [3H]spiperone as the ligand and 10 mM dopamine hydrochloride was used in blanks. Spiperone binding sites were characterized in a 40-week-old foetal brain to be dopamine receptors by the following criteria: (1) It was localized in a crude mitochondrial pellet that included synaptosomes; (2) binding was saturable at 0.8 nM concentration; (3) dopaminergic antagonists spiperone, haloperidol, pimozide, trifluperazine and chlorpromazine competed for the binding with IC50 values in the range of 0.3–14 nM while agonists—apomorphine and dopamine gave IC50 values of 2.5 and 10 μM, respectively suggesting a D2 type receptor.Epinephrine and norepinephrine inhibited the binding much less efficiently while mianserin at 10 μM and serotonin at 1 mM concentration did not inhibit the binding. Bimolecular association and dissociation rate constants for the reversible binding were 5.7 × 108 M−1 min−1 and 5.0 × 10−2 min−1, respectively. Equilibrium dissociation constant was 87 pM and the KD obtained by saturation binding was 73 pM.During the foetal age 16 to 40 weeks, the receptor concentration remained in the range of 38–60 fmol/mg protein or 570–1080 fmol/g striatum but it increased two-fold postnatally reaching a maximum at 5 years Significantly, at lower foetal ages (16–24 weeks) the [3H]spiperone binding sites exhibited a heterogeneity with a high (KD, 13–85 pM) and a low (KD, 1.2–4.6 nM) affinity component, the former accounting for 13–24% of the total binding sites. This heterogeneity persisted even when sulpiride was used as a displacer. The number of high affinity sites increased from 16 weeks to 24 weeks and after 28 weeks of gestation, all the binding sites showed only a single high affinity.GTP decreased the agonist affinity as observed by dopamine competition of [3H]spiperone binding in 20-week-old foetal striata and at all subsequent ages. GTP increased IC50 values of dopamine 2 to 4.5 fold and Hill coefficients were also increased becoming closer to one suggesting that the dopamine receptor was susceptible to regulation from foetal life onwards.