Propyl-2-(8-(3,4-Difluorobenzyl)-2 `,5 `-Dioxo-8-AzaspiroBicyclo3.2.1] Octane-3,4 `-Imidazolidine]-1 `-yl) Acetate Induces Apoptosis in Human Leukemia Cells through Mitochondrial Pathway following Cell Cycle Arrest

Background: Due to the functional defects in apoptosis signaling molecules or deficient activation of apoptosis pathways, leukemia has become an aggressive disease with poor prognosis. Although the majority of leukemia patients initially respond to chemotherapy, relapse is still the leading cause of death. Hence targeting apoptosis pathway would be a promising strategy for the improved treatment of leukemia. Hydantoin derivatives possess a wide range of important biological and pharmacological properties including anticancer properties. Here we investigated the antileukemic activity and mechanism of action of one of the potent azaspiro hydantoin derivative, (ASHD). Materials and Methods: To investigate the antileukemic efficacy of ASHD, we have used MTT assay, cell cycle analysis by FACS, tritiated thymidine incorporation assay, Annexin V staining, JC1 staining and western blot analysis. Results: Results showed that ASHD was approximately 3-fold more potent than the parent compounds in inducing cytotoxicity. Tritiated thymidine assay in conjunction with cell cycle analysis suggests that ASHD inhibited the growth of leukemic cells. The limited effect of ASHD on cell viability of normal cells indicated that it may be specifically directed to cancer cells. Translocation of phosphatidyl serine, activation of caspase 3, caspase 9, PARP, alteration in the ratio of BCL2/BAD protein expression as well as the loss of mitochondrial membrane potential suggests activation of the intrinsic pathway of apoptosis. Conclusion: These results could facilitate the future development of novel hydantoin derivatives as chemotherapeutic agents for leukemia.

Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents

A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lilies (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 mu M). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.

Optical, Electrochemical, and Structural Properties of Spray Coated Dihexyl Substituted Poly (3,4 propylene dioxythiophene) Film for Optoelectronics Devices

The dihexyl substituted poly (3,4-propylenedioxythiophene) (PProDOT-Hx(2)) thin films uniformly deposited by cost effective spray coating technique on transparent conducting oxide coated substrates. The electro-optical properties of PProDOT-Hx(2) films were studied by UV-Vis spectroscopy that shows the color contrast about 45% with coloration efficiency of approximate to 185cm(2)/C. The electrochemical properties of PProDOT-Hx(2) films were studied by cyclic voltammetry and AC impedance techniques. The cyclic voltammogram shows that redox reaction of films are diffusion controlled and ions transportation will be faster on the polymer film at higher scan rate. Impedance spectra indicate that polymer films are showing interface charge transfer process as well as capacitive behavior between the electrode and electrolyte. The XRD of the PProDOT-Hx(2) thin films revealed that the films are in amorphous nature, which accelerates the transportation of ions during redox process.

Specroelectrochemical, Switching Kinetics, and Chronoamperometric Studies of Dibenzyl Derivative of Poly(3,4-propylenedioxythiophene) Thin-Film-Based Electrochromic Device

The dibenzyl derivative of poly(3,4-propylenedioxythiophene) (PProDOT-Bz(2)) thin film is deposited onto ITO-coated glass substrate by electropolymerization technique. The electropolymerization of ProDOT-Bz(2) is carried out by a three-electrode electrochemical cell. The cyclic voltammogram shows the redox properties of electrochemically prepared films deposited at different scan rates. The thin films prepared were characterized for its morphological properties to study the homogeniety. Classic six-layer structure of PProDOT-Bz(2) electrochromic device using this material was fabricated and reported for the first and its characterizations such as spectroelectrochemical, switching kinetics, and chronoamperometric studies are performed. The color contrast of the thin film and the device achieved are 64 and 40%, respectively, at lambda(max) (628 nm). The switching time is recorded and the observed values are 5 s from the coloring state to the bleaching state and vice versa. The chronoamperometry shows that the device performed up to 400 cycles, and it is capable of working up to 35 cycles without any degradation. (C) 2014 Wiley Periodicals, Inc.

2-(4-Chlorobenzyl)-6-arylimidazo2,1-b]1,3,4]thiadiazoles: Synthesis, cytotoxic activity and mechanism of action

The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo2,1-b]1,3,4]wthiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo2,1-1)]1,3,4]th iadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-ypimidazo2,1-1)]1,3,4]thi adiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. (C) 2014 Elsevier Masson SAS. All rights reserved.

Synthesis and antiproliferative activity of imidazo2,1-b]1,3,4]thiadiazole derivatives

A series of 2,5,6-substituted imidazo2,1-b]1,3,4]thiadiazole derivatives have been prepared and were tested for antiproliferative activity on cancer cells at the National Cancer Institute. Results showed that molecules with a benzyl group at position 2, exhibited an increase in activity for the introduction of a formyl group at the 5 position. The compound 2-benzyl-5-formyl-6-(4-bromophenyl)imidazo 2,1-b]1,3,4]thiadiazole 22 has been chosen for understanding the mechanism of action by various molecular and cellular biology studies. Results obtained from cell cycle evaluation analysis, analysis of mitochondrial membrane potential and Annexin V-FITC by flow cytometric analysis, ROS production and expression of apoptotic and DNA-repair proteins suggested that compound 22 induced cytotoxicity by activating extrinsic pathway of apoptosis, however, without affecting cell cycle progression. (C) 2014 Elsevier Ltd. All rights reserved.

One-step synthesis of a cyclic 2,17-dioxo3,3](4,4 `)biphenylophane and first preparation of a microporous polymer network from a macrocyclic precursor by cyclotrimerization

One-step synthesis of a cyclic 2,17-dioxo3,3](4,4') biphenylophane (MC) was achieved in high yield; its structure was verified by single crystal X-ray analysis. As a first example, a microporous polymer network was formed from macrocycle MC via acid-catalysed cyclotrimerization yielding a BET surface area of ca. 570 m(2) g(-1).

Synthesis and evaluation of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles as anti-cancer agents

A series of 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazoles 9a-j were obtained via multistep synthesis from hydroxybenzophenones 4a-e. The cytotoxicity of compounds 9a-j was evaluated against human leukemia cell lilies (K562 and CEM). The compounds exhibited moderate to good anti-cancer activity with compounds 9b and 9i having a chloro group exhibiting the best activity (IC50 = 10 mu M). Compound 9i exhibited activity against both the cell lines and 9b only exhibited activity against CEM. Further, a lactate dehydrogenase (LDH) assay and DNA fragmentation studies of the compounds 9a-j were also performed. (C) 2013 Elsevier Masson SAS. All rights reserved.

Synthesis of Optically Active 2-Amino-1,3,4-oxadiazoles and their Hybrid Peptides

Synthesis of 2-amino-1,3,4-oxadiazole derivatives of N-Cbz(benzyloxycarbonyl)/Boc-protected amino/peptide acids under sonication is described. The conditions involved in the present protocol are simple, mild, and racemization free. The utility of 2-amino group in the substituted oxadiazoles for the incorporation of peptide and ureido bonds to obtain hybrid peptidomimetics is also delineated. The 2-amino-1,3,4-oxadiazole 3b was obtained as a single crystal, and its molecular structure has been confirmed through X-ray crystallographic study.

Crystal chemistry and photomechanical behavior of 3,4-dimethoxycinnamic acid: correlation between maximum yield in the solid-state topochemical reaction and cooperative molecular motion

A new monoclinic polymorph, form II (P2(1)/c, Z = 4), has been isolated for 3,4-dimethoxycinnamic acid (DMCA). Its solid-state 2 + 2 photoreaction to the corresponding alpha-truxillic acid is different from that of the first polymorph, the triclinic form I (P (1) over bar, Z = 4) that was reported in 1984. The crystal structures of the two forms are rather different. The two polymorphs also exhibit different photomechanical properties. Form I exhibits photosalient behavior but this effect is absent in form II. These properties can be explained on the basis of the crystal packing in the two forms. The nanoindentation technique is used to shed further insights into these structure-property relationships. A faster photoreaction in form I and a higher yield in form II are rationalized on the basis of the mechanical properties of the individual crystal forms. It is suggested that both Schmidt-type and Kaupp-type topochemistry are applicable for the solid-state trans-cinnamic acid photodimerization reaction. Form I of DMCA is more plastic and seems to react under Kaupp-type conditions with maximum molecular movements. Form II is more brittle, and its interlocked structure seems to favor Schmidt-type topochemistry with minimum molecular movement.

Efecto al aplicar tres dosis de vermicompost con fertilización foliar complementaria en el crecimiento y rendimiento del plátano (Musa paradisiaca L.) variedad CEMSA 3/4, UNA, 2011 - 2013

El trabajo de investigación consistió en el establecimiento del cultivo de plátano variedad CEMSA ¾ en la parcela agroecológica de cultivos perennes del Departamento de Producción Vegetal (DPV) de la Universidad Nacional Agraria, ubicada en el km 12 ½ carretera norte , Managua. Se aplicaron tres dosis de vermicompost (15, 30 y 45 t ha - 1 ) equivalente a 6, 12 y 18 kg planta - 1 con fertilización foliar complementaria : enraizador ( 50 g ) , completo 20 - 20 - 20 ( 40 g ) y sulfato de magnesio ( 20 g) por cada 20 l de agua. Se evaluaron variables de crecimiento: Altur a de la planta (m), Diámetro del pseudotallo (cm), Número de hojas funcionales a cosecha, Área f oliar (m 2 ) y variables de rendimiento: Peso del racimo (kg), Número total de manos, Número de dedos del racimo a cosecha, Diámetro de los dedos (cm ) , Diámetro d el raquis (cm) , Largo de los dedos (cm) y Largo del racimo (cm) . Se estableció en un diseño de parcelas apareadas formadas por tres franjas, con una población inicial de 180 plantas a una distancia de 2 m entre planta y 2 m entre surco. El tratamiento a 2 b 1 (30 t ha - 1 + enraizador) , obtuvo los mejores resultados en las variables altura de planta (2.1 m), diámetro del pseudotallo (105 . 94 cm) y número de hijos (3.8), no así en la variable área foliar donde el tratamiento a 1 b 2 (15 t ha - 1 + enraizador + completo 20 - 20 - 20) fue el que mostró mayor área foliar (8 .54 m²). Los rendimientos obtenidos en el tratamiento a 2 b 1 (30 t ha - 1 + enraizador) presentaron mejor resultado en las variables peso de racimo (10.46 kg), n ú mero de manos (9.06) y número de dedos (46.59). E n el diámetro del dedo se destacó el tratamiento a 3 b 3 (30 t ha - 1 + enraizador + completo 20 - 20 - 20 y sulfato de magnesio) con 4.58 cm y 4.37 cm respectivamente. En el largo del dedo se destacaron los tratamientos a 1 b 1 (15 t ha - 1 + enraizador) y a 1 b 3 (15 t ha - 1 + enraizador + completo 20 - 20 - 20 y sulfato de magnesio) con 30.13 cm y 24.36 cm respectivamente. El análisis económico demostró que el tratamiento que present ó mayor rentabilidad es el a 2 b 1 en base a la relación beneficio - costo se genera una ganancia de C$ 1 .17 por cada córdoba invertido

Micropropagación tradicional y en biorreactores económicos de inmersión temporal del cultivar de plátano (Musa spp.) CEMSA 3/4

El estudio se realizó en el laboratorio de cultivo de tejidos de la Universidad Nacional Agraria de marzo 2014 - j unio de 2015 . Se evaluó el efecto del AIA y del BAP en el establecimient o d el plátano cv CEMSA ¾ , l a respuesta de los tejidos a los medios de cultivo de consistencia semi - sólida en tres subcultivos sucesivos en la multiplicación y la producción de brotes axilares por efecto de la siembra de 30, 35, 40, 45 y 50 tejidos por BEIT . S e evaluó el efecto del AIA y de los BEIT en la inducción de raíces . Los datos de establecimiento se analizaron en tablas porcentuales, en las fases de multiplicación y enraizamiento el diseño bloques completos al azar y se determinaron los mejores trata mientos mediante el comportamiento estadístico de las medias mediante el análisis de Duncan y Waller. Los ápices respondieron favorablemente cuando se adicionaron concentraciones entre 0.50 y 1 mg l - 1 de AIA o el suministro de 1 mg l - 1 de BAP, la producció n de fenoles se relacionó con el genotipo . Las ma y ores medias de brot ación axilar en el terce r subcultivo cuando se agregó 3 mg l - 1 de BAP con o sin adición de AIA . Con densidades de siembra de 30, 40, 45 y 50 yemas axilares por BEIT no se registraron dife rencias significativas en el número de brotes axilares. La longitud del pseudotallo, el número de hojas y el número de raíces respondieron favorablemente a las sales de MS enriquecidas con concentraciones de 0.25, 0.50 ó 0.75 mg l - 1 de AIA

以1-苯基-3-甲基-4-苯甲酰基代吡唑酮[5]萃取稀土和钍铀钛锆及其在分析化学中的某些应用

本文研究了以PMBP-苯萃取稀土和钍、铀、钛、锆的萃取行为。测定了La、Ce、Pr、Nd、Sm、Gd、Dy、Yb、Y、U(Ⅵ)、Ti、Th和Zr的pH_(1/2)值,计算了它们的萃取平衡常数。并介绍了近十年来作者将此萃取剂应用于铀、钍、稀土、鋰、钢铁合金及岩石中痕量稀土、钍和钙的分离和测定方面的工作。实践证明,PMOP合成简便、价格低廉、萃取能力较强,是比TTA更为优越的萃取剂。