Synthesis,characterization and biological evaluation of some novel sulfonylthiosemicarbazides

Abstract

A series of thiosemicarbazides were synthesized and structurally characterized by spectroscopic techniques (NMR, FT-IR) besides elemental analysis. These compounds were evaluated for their cytotoxicity against human breast cancer cell line MCF7 and prostate cancer cell line PC3 and nonmalignant fibroblast L929 cell line by MTT assay. Among the compounds, N-[2-(4-chlorophenyl)ethyl]-2-[(4-methylphenyl)sulfonyl]hydrazinecarbothioamide (3d) and 2-[(4-methylphenyl)sulfonyl]-N-[4-(trifluoromethoxy)phenyl]hydrazinecarbothioamide (3f) were found to display significant cytotoxicity with IC₅₀ of 13.87?μM (against PC3 cell line) and 1.47?μM (against MCF7 cell line), respectively. These compounds were non-cytotoxic to normal cell line with IC₅₀>100?μM. Western blotting studies demonstrated that compound 3f induced apoptosis and caused cell death in the MCF7 and PC3 cell lines via an increase in Bax protein expression and a slight decrease in Bcl-2 protein expression. The gene expression ratio Bax/Bcl-2 showed the induction of mitochondrial apoptosis in cancer cell lines. All of synthesized compounds have also been tested for antioxidant activity and all compounds achieved strong inhibition of the DPPH radical. These findings showed that compound 3f, displays potential to be further explored in the development of new anticancer agents.     

The Synthesis of Novel Macrocycles,Part V. The Coumarin Crown Ethers and Cation Binding with Fluorescence Spectra

Abstract

The 4-H, 4-methyl and 4-phenyl derivatives of benzo-α-pyrone of 12-crown-4 and 15-crown-5 were synthesised starting from 4-substituted-6,7-dihydroxy- and 7,8-dihydroxybenzo-α-pyrones which reacted with dichloropolyethylene glycols in DMF/water/alkali carbonate. The coumarin-macrocycles were identified by elemental analysis, IR, EI-GC-MS as well as ¹H, ¹³C NMR spectroscopy. The full experimental and spectral data is reported along with ion binding data studied in acetonitrile using fluorescence spectroscopy. The binding of the fluorogenic coumarin-crowns with Li⁺, Na⁺ and K⁺ were recognized as specific alterations on their fluorescence spectra that strongly originated from the structures. The observed CEQFS depending on the bound cation radii and macrocycle size evidenced the rules of cationic recognition of macrocycles. Some 15-crown-5 derivatives exhibited interesting Li⁺ and Na⁺ binding selectivities.     

The cytotoxic activities of imidazole derivatives prepared from various guanylhydrazone and phenylglyoxal monohydrate

Abstract

A series of imidazole derivatives were synthesized from two-component condensation reaction of phenylgloxal monohydrate with guanylhydrazone. They were characterized by spectroscopic and analytical techniques. The in vitro anticancer evaluation of these compounds was done on human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines using the MTT assay method. Most of the newly synthesized compounds displayed cytotoxic activity against these cancerous cells. In fact, compounds 3a, 3e, and 3?h exhibited more cytotoxic activities than the positive control drugs, fluro-5, and irinocam, against the MCF-7 cell line. Almost all the compounds, except for three, 3b, 3d, and 3f, gave more cytotoxic results than cisplatin. Therefore, these compounds could be considered for further development as anticancer drug candidates.     

Investigation of radiocesium biokinetics in Manila clam (Ruditapes philippinarum)

This study was carried out to better understand the biokinetics of radiocesium in clams living in sediment. The accumulation and depuration kinetics of ¹³⁴Cs were investigated in the Manila clam (Ruditapes philippinarum) under controlled laboratory conditions. The concentration factor was found to be 3.0 for ¹³⁴Cs in the whole body; however, the concentration factor in the soft part of the clams (12) was significantly higher than those in the whole body and shell (0.80). The depuration kinetics of the radionuclide were described by a two-component exponential model for the whole body. The biological half-lives in the fast and slow components were found to be 0.63 and 22.1 days, respectively. The depuration kinetics for ¹³⁴Cs in the soft parts were described by a single-component exponential model with a resultant the biological half-life of 18.0 days.     

Reversible Immobilization of Urease by Using Bacterial Cellulose Nanofibers

In this work, bacterial cellulose nanofibers were produced by using the Gluconacetobacter hansenii HE1 strain. These nanofibers were derivatized with dye affinity ligand Reactive Green 5, and these newly synthesized dye-attached nanofibers were used for affinity adsorption of urease. Reactive Green 5-attached nanofibers were characterized by Fourier transform infrared spectroscopy, SEM, and energy-dispersive x-ray spectroscopy analysis. Some adsorption conditions which significantly affect the adsorption efficiency were investigated. The maximum urease adsorption capacity was found to be 240 mg/g nanofiber in pH 6.0 and at room temperature. Dye-free plain nanofibers also used for studying nonspecific urease adsorption onto plain nanofibers and nonspecific adsorption were found to be negligible (3.5 mg/g nanofiber). Prepared dye-attached nanofibers can be used in five successive adsorption/desorption steps without any decrease in their urease adsorption capacity. The desorption rate of the adsorbed urease was found to be 98.9 %. The activity of the urease was also investigated, and it was found that free and desorbed urease from the dye-attached nanofibers showed similar specific activity.     

Novel anhydrous proton conducting copolymers of 1‐vinyl‐1,2,4‐triazole and diisopropyl‐p‐vinylbenzyl phosphonate

Phosphonic acid functional polymers are currently of interest because of their high proton conductivity in humidified and anhydrous systems. In addition, heterocyclic compounds are used in anhydrous proton conducting polymer membranes. In that study, a new copolymer based on 1‐vinyl‐1,2,4‐triazole (VTri) and diisopropyl‐p‐vinylbenzyl phosphonate (VBP) was synthesized, and their thermal, chemical, and proton conducting properties were investigated. The copolymers were synthesized by free radical copolymerization of the corresponding monomers at several monomer feed ratios to obtain P(VTri‐co‐VBP) copolymers. The copolymer samples were then hydrolyzed to produce poly(vinyl triazole‐co‐vinyl phosphonic acid) copolymers. The composition of the copolymers was determined by elemental analysis. The copolymerization and hydrolysis reactions were verified by Fourier transform infrared spectroscopy and ion exchange capacity measurements. Thermogravimetry analysis indicates that the copolymers are thermally stable up to 300°C. In order to increase the proton conductivity, the copolymers were doped with H₃PO₄ at several stoichometric ratios. The proton conductivity increases with triazole and phosphoric acid content. In the absence of humidity, the copolymer electrolyte, P(VTri‐co‐VBPA)1:0.5 X = 2, showed a proton conductivity of 0.005 S/cm at 150°C. Copyright © 2013 John Wiley & Sons, Ltd.     

Spectroscopy and X-ray studies of {{6,6′-dimethoxy-2,2′-[ethane-1,2-diyl-bis-(nitrilomethylidyne)]diphenolato}(aqua)-dioxouranium(VI)} dehydrate

The C₁₈H₂₀N₂O₇U · 2H₂O (I) complex has been prepared and characterized by single crystal X-ray diffraction properties (CIF file CCDC no. 913243). The title compound crystallizes in the orthorhombic system, space group Pbca with a = 19.542(5), b = 9.916(5), c = 21.940(5) Å, V = 4252(3) ų and Z = 8. In complex I, the U atom has a distorted pentagonal-bipyramidal geometry with a tetradentate Schiff base ligand and water molecule in the equatorial plane and oxo atoms in the axial positions. The crystal packing occurs intra-inter molecular hydrogen bonds.     

Strong ionic interactions in noncovalent complexes between poly(ethylene imine), a cationic electrolyte,and Cibacron Blue,a nucleotide mimic – implications for oligonucleotide vectors

Cationic polymers can bind DNA to form polyplexes, which are noncovalent complexes used for gene delivery into the targeted cells. For more insight on such biologically relevant systems, the noncovalent complexes between the cationic polymer poly(ethylene imine) (PEI) and the nucleotide mimicking dye Cibacron Blue F3G‐A (CB) were investigated using mass spectrometry methods. Two PEIs of low molecular weight were utilized (M_n ≈ 423 and 600 Da). The different types of CB anions produced by Na⁺/H⁺ exchanges on the three sulfonic acid groups of CB and their dehydrated counterparts were responsible for complex formation with PEI. The CB anions underwent noncovalent complex formation with protonated, but not with sodiated PEI. A higher proportion of cyclic oligomers were detected in PEI423 than PEI600, but both architectures formed association products with CB. Tandem mass spectrometry studies revealed a significantly stronger noncovalent interaction between PEI and dehydrated CB than between PEI and intact CB. Copyright © 2014 John Wiley & Sons, Ltd.     

A new type of monodisperse porous, hydrophilic microspheres with reactive chloroalkyl functionality: synthesis and derivatization properties

A seeded polymerization method based on a new functional monomer, 3-chloro-2-hydroxypropyl methacrylate (HPMA-Cl), was proposed for the synthesis of a new type of monodisperse porous, hydrophilic microspheres with reactive character. By applying the method, poly(3-chloro-2-hydroxypropyl methacrylate-co-ethylene dimethacrylate) (poly(HPMA-Cl-co-EDMA)) microspheres in the range of 4–7 μm, with specific surface areas between 2 and 146 m²/g, were obtained. The microspheres are hydrophilic in nature due to the hydroxyl groups and are easily derivatizable due to the reactive chloropropyl moiety. Ligands in the form of small molecules carrying hydrophobic alkyl or hydrophilic ion exchanger groups were covalently attached onto the microspheres via simple and one-pot reactions via their chloropropyl functionality. Using the same functionality, click chemistry and surface-initiated atom transfer radical polymerization were also applied for the generation of triazole ring and zwitterionic molecular brushes on the microspheres, respectively. Poly(HPMA-Cl-co-EDMA) microspheres seem to be a promising hydrophilic reactive material particularly for the synthesis of ion exchanger resins and chromatographic stationary phases.     

Unusual products in the reactions of hexachlorocyclotriphosphazatriene with sodium aryloxides

Reactions of hexachlorocyclotriphosphazatriene, N₃P₃Cl₆ 1 , with sodium aryloxides have been studied. Compound 1 was found to react by the nucleophilic substitution pathway to yield monocyclophosphazenes [N₃P₃Cl₆(OC₆H₂Bu¹₃-2,4,6) 5 and N₃P₃Cl₄(OC₆H₂Me-4-Bu¹₂-2,6)₂ 6 ] and bi(cyclophosphazenes) ([Cl₅N₃P₃-P₃N₃Cl₄(OC₆H₃Bu¹₂-2,6)] 7 and [N₃P₃(OC₆H₃Bu¹₂-2,6)₅]₂ 8 ). The unusual bi(cyclophosphazenes) 7 and 8 are the first examples of two cyclotriphosphazene rings linked by a P(SINGLE BOND)P bond [2.193 (2) Å], which have been obtained by reacting 1 with ArONa. The structures of compounds 5–8 are ascertained by elemental analyses, ¹H-, ³¹P-¹³C-NMR, IR, and MS spectra. The molecular structure of monocyclic-phosphazene 5 was determined by X-ray diffraction techniques for further structural assignment. It crystallizes in the monoclinic space group P2₁/m with a = 6.144(2), b = 17.079(9), c = 13.181(9) Å, β = 92.79(7), and Z = 2, R = 0.074. Compound 5 is on a crystallographic mirror plane, and there is only a half molecule in the asymmetric unit. © 1996 John Wiley & Sons, Inc.