(Triazinediyl)bis sulfamic acid-functionalized silica-coated magnetite nanoparticles: Preparation,characterization and application as an efficient catalyst for synthesis of mono-, bis-, tris- and spiro-perimidines

(Triazinediyl)bis sulfamic acid-functionalized silica-coated magnetite nanoparticles have been prepared and applicated as an efficient catalyst for synthesis of mono-, bis-, tris- and spiro-perimidines. The desired products have been synthesized in high purity and good yields. The workup procedure of reaction is simple. The catalyst was easily separated from the reaction mixture with the assistance of an external magnetic field and reused for several runs without deterioration in catalytic activity. The core/shell nanoparticles were characterized by transmission electron microscopy, scanning electron microscope, powder X-ray diffraction, energy dispersive spectrometer, Fourier transform infrared spectroscopy and vibrating sample magnetometer.     

Two copper(II) complexes of curcumin derivatives: synthesis,crystal structure and in vitro antitumor activity

Two Cu(II) complexes of curcumin derivatives, formulated as CuL ₂ ^a (1) and CuL ₂ ^b (2) [HL^a = 1,7-bis(4-ethyloxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione and HL^b = 1,7-bis(4-butyloxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione], have been synthesized and characterized by single-crystal X-ray diffraction, along with physicochemical and spectroscopic methods. In both complexes, each Cu(II) center is surrounded by four oxygen atoms from two β-diketone ligands in a square planar geometry. Complex 1 forms a 2D layer structure through intermolecular π–π stacking interactions, as well as weak coordination interactions between the Cu and O atoms of the solvent 1,4-dioxane molecules. Complex 2 displays a 1D column structure stabilized by intermolecular π–π stacking interactions. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays were used to evaluate the cytotoxicities of these complexes against three human cancer cell lines. The results show that the Cu(II) complexes exhibit more potent inhibition tumor growth in comparison with the free ligands.     

Linear diacetylene polymers containing bis(dimethylsilyl) phenyl and/or bis-(tetramethyldisiloxane) carborane residues: Their synthesis,characterization and thermal and oxidative properties

A series of inorganic-organic linear diacetylenic hybrid polymers ( 5a–e ) were prepared by the polycondensation reaction of 1,4-dilithiobutadiyne with 1,4-bis(dimethylchlorosilyl)benzene and/or 1,7-bis(tetramethylchlorodisiloxane)-m-carborane. Their structures were characterized using FTIR, and ¹³C and ¹H NMR spectroscopies, and their thermal and oxidative properties were evaluated by DSC and TGA analyses. The hybrid polymers exhibited solubility in common organic solvents and were viscous liquids or low melting solids at room temperature. Broad prominent exotherms, attributed to reaction of the diacetylenic units, were observed by DSC in the 306°C to 354°C temperature range. When 5a–e were analyzed by TGA to 1000°C under nitrogen, weight retention between 79 and 86% were obtained. Ageing studies, performed at elevated temperatures in air on a thermoset and a ceramic obtained from polymer 5b , showed this system to have excellent thermal and oxidative stability. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2387–2391, 1997     

Design,synthesis and biological evaluation of novel arylpiperazine derivatives on human prostate cancer cell lines

A series of novel arylpiperazine derivatives was synthesized. The in vitro cytotoxic activities of all synthesized compounds against three human prostate cancer cell lines(PC-3, LNCa P, and DU145) were evaluated by a CCK-8 assay. Compounds 8, 10, 13, 17 and 20 exhibited strong cytotoxic activities against the tested cancer cell lines(IC_(50)3 μmol/L). In addition, these compounds exhibited weak cytotoxic effects on human epithelial prostate normal cells WPMY-1. The structure–activity relationship(SAR) of these arylpiperazine derivatives was also discussed based on the obtained experimental data.     

Two Cu(I) complexes based on semicarbazone ligand: synthesis,crystal structure,Hirshfeld surface and anticancer activity evaluation against human cell lines

Structural Chemistry - Two novel Cu(I) complexes with the 2-acetylpyridine-N(4)-phenyl semicarbazone (HL) ligand, [CuCl (HL)(PPh3)]∙CH3CN (1) and [CuBr (HL)(PPh3)] (2), were investigated by...     

Bithiophene-Cored,mono-, bis-, and tris-(Trimethylammonium)-Substituted,bis-Triarylborane Chromophores: Effect of the Number and Position of Charges on Cell Imaging and DNA/RNA Sensing

The synthesis, photophysical, and electrochemical properties of selectively mono-, bis- and tris-dimethylamino- and trimethylammonium-substituted bis-triarylborane bithiophene chromophores are presented along with the water solubility and singlet oxygen sensitizing efficiency of the cationic compounds Cat¹⁺ , Cat²⁺ , Cat(i)²⁺ , and Cat³⁺ . Comparison with the mono-triarylboranes reveals the large influence of the bridging unit on the properties of the bis-triarylboranes, especially those of the cationic compounds. Based on these preliminary investigations, the interactions of Cat¹⁺ , Cat²⁺ , Cat(i)²⁺ , and Cat³⁺ with DNA, RNA, and DNApore were investigated in buffered solutions. The same compounds were investigated for their ability to enter and localize within organelles of human lung carcinoma (A549) and normal lung (WI38) cells showing that not only the number of charges but also their distribution over the chromophore influences interactions and staining properties.     

Design,synthesis and antiproliferative activity against human cancer cell lines of novel benzo-, benzofuro-, azolo- and thieno-1,3-thiazinone resorcinol hybrids

In this paper we report the design and synthesis of novel derivatives of the 4H-3,1-benzothiazinone type and heterocyclic analogues, i.e. benzofuro-, azolo- and thieno-1,3-thiazin-4-ones possessing 2,4-dihydroxyphenyl substituent. The compounds were obtained by the one-step reaction of aminobenzamides or heterocyclic aminocarboxamides with aryl-modified sulfinylbis[(2,4-dihydroxyphenyl)methanethione]. Evaluation of their antiproliferative potency against human cancer cell lines showed that the activity of some analogues was similar to that of cisplatin. The highest activity and low toxicity were found for 6-tert-butyl-2-(5-chloro-2,4-dihydroxyphenyl)-4H-thieno[3,2-d][1,3]thiazin-4-one. The structure–activity elucidation reveals that the most active compounds are those with a thienothiazin-4-one and benzofuro[3,2-d][1,3]thiazin-4-one skeleton and the presence of the hydrophobic substituent (Et, Cl) in the benzenediol moiety increases their antiproliferative potency. The ADMET properties of selected compounds including metabolic stability and toxicity profile were estimated in silico.     

Novel ammonium phosphinates containing peptide moiety: Synthesis, structure, and in vitro antimicrobial activity

Five new ammonium phosphinates with formula [XC₆H₄NHC(O)NHP(O)YO]^?[H₂Y]⁺ (Y = N(CH₃)(CH₂C₆H₅), X = H (IV), CH₃ (V), NO₂ (VI); Y = NH(CH₂C₆H₅), X = H (VII), NO₂ (VIII)) were synthesised by the reaction of N-arylureidophoshoryl dichlorides with N-methylbenzylamine or benzylamine in the presence of an excess amount of the corresponding amine. All new compounds were characterised by NMR and IR spectral data and elemental analysis. Their antimicrobial activity was tested against some Gram-positive and Gram-negative bacteria and fungi. Compounds IV and VIII exhibited moderate activity in vitro against Bacillus subtilis. In addition, compound VIII moderately inhibited Pseudomonas aeruginosa. The crystal structure of benzylmethylammonium(3-phenylureido)(benzylmethylamino)phosphinate (IV) was also determined. This compound crystallises in the orthorhombic system.     

Di‐n‐butyltin aminoarylcarboxylates: structure,properties and in vitro antitumor activity

The properties and structures of the tetranuclear dibutyltin complexes [Sn₄(µ₃‐O)₂(C₄H₉‐n)₈­{OOCC₆H₃(NH₂)₂‐3,4}₄] (1), [Sn₄(µ₃‐O)₂(C₄H₉‐n)₈{OOCC₆H₃(NH₂)₂‐3,5}₄] (2), [Sn₄(µ₃‐O)₂(C₄H₉‐n)₈­{OOC‐2‐C₆H₄N?NC₆H₄N(CH₃)₂‐4}₄] (3) are described. Complex 3 adopts a structure with a tetranuclear Sn₄(µ₃‐O)₂ core. All tin atoms are five‐coordinate and form bonds with three oxygen atoms and two butyl ligands. Two carboxylates are bridging and two are terminal ligands. IR and NMR spectra indicate that the same structure is adopted by complexes 1 and 2. The molecular and electronic structures of complex 1 of C _i symmetry have been studied using the semi‐empirical PM3 formalism. The calculated structure and bond distances agree with X‐ray data. All complexes are effective antitumor agents. Copyright © 2002 John Wiley & Sons, Ltd.     

Structural aspects of a trimetallic CuII derivative: cytotoxicity and anti-proliferative activity on human cancer cell lines

A trimetallic Cu^II derivative, [Cu₃(L)₂(CF₃COO)₂] (1) (where H₂L = N,N′-bis(salicylidene)-1,3-propanediamine), was prepared and characterized. In 1, the two terminal Cu^II ions are linked to the central Cu^II by trifluoroacetato and doubly bridging phenoxido. Both the square-pyramidal and octahedral geometries are observed among two different Cu^II centers in the linear arrangement of the trimetallic unit. Compound 1 is characterized by IR and UV-Vis spectra. Compound 1 has high cytotoxic activity in breast adenocarcinoma (MCF-7), colorectal carcinoma (HCT116) and particularly, in ovarian carcinoma (A2780) cell line compared to a lung adenocarcinoma cell line. The IC₅₀ in A2780 cells is 25 times lower than the respective value for normal human primary fibroblasts demonstrating 1 has higher cytotoxicity towards cancer cells. Additionally, combination of DOX with 1 induces a higher loss of HCT116 cell viability compared with each drug alone.     

Echinophora tenuifolia L. branches phytochemical profile and antiproliferative activity on human cancer cell lines

Abstract

The methanolic extract of Echinophora tenuifolia L. branches and its fractions were evaluated for their in vitro cell growth inhibitory activity on different human cancer cell lines (C32, LoVo and SKBr3) and the normal BJ fibroblasts. All tested samples were effective against the melanoma cell line C32, with IC₅₀ values ranging from 22.8?±?0.8 to 78.7?±?1.2?μg/mL, the antiproliferative activity of the dichloromethane fraction being significantly higher. This fraction was also effective against the LoVo adenocarcinoma cell line, with an IC₅₀ value of 53.0?±?2.1?μg/mL. The ethyl acetate and dichloromethane fractions showed the highest lipid peroxidation inhibitory activity, verified by means of the β-carotene bleaching test. The phytochemical profiles of E. tenuifolia branches extract were established by means of GC-MS and HPTLC. Overall, branches of E. tenuifolia L. could represent a rich source of bioactive compounds, potentially useful in the pharmaceutical field.     

Proteomic analysis of laser capture microdissected human prostate cancer and in vitro prostate cell lines

Specific populations of normal and malignant epithelium from three radical prostatectomy tissue specimens were procured by laser capture microdissection (LCM) and analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Six proteins that were only seen in malignant cells and two proteins that were only seen in benign epithelium were reproducibly observed in two of two cases examined. Furthermore, these proteins were not observed in the 2-D PAGE profiles from the patient-matched microdissected stromal cell populations, but were seen in the protein profiles from the undissected whole cryostat sections. One of these proteins was determined to be prostate-specific antigen (PSA) by Western blot analysis, and intriguingly the remaining protein candidates were found to be at least as abundant as the PSA protein. Comparison of 2-D PAGE profiles of microdissected cell with matched in vitro cell lines from the same patient, and metastatic prostate cancer cell lines (LnCaP and PC3) showed striking differences between prostate cells in vivo and in vitro with less than 20% shared proteins. The data demonstrate that 2-D PAGE analysis of LCM-derived cells can reliably detect alterations in protein expression associated with prostate cancer, and that these differentially expressed proteins are produced in high enough levels which could allow for their clinical utility as new targets for therapeutic intervention, serum markers, and/or imaging markers.     

New sorafenib derivatives: synthesis, antiproliferative activity against tumour cell lines and antimetabolic evaluation

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a-e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a-e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a-e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a-e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a-e (IC(50) = 1-4.3 μmol·L-1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.     

New heteroleptic palladium(II) dithiocarbamates: synthesis,characterization, packing and anticancer activity against five different cancer cell lines

Two new heteroleptic palladium(II) complexes have been synthesized by reacting equimolar quantities of palladium(II) chloride, sodium 4‐(2‐methoxyphenyl)piperazine‐1‐carbodithioate and diphenyl‐p‐tolylphosphine ( 1 ) or tri‐p‐tolylphosphine ( 2 ). Complexes 1 and 2 have been characterized using elemental analysis, Fourier transform infrared spectroscopy, multinuclear NMR (¹H, ¹³C and ³¹P) spectroscopy and single‐crystal X‐ray analysis. The latter technique confirms a pseudo square‐planar geometry in which two adjacent positions are occupied by bidentate dithiocarbamate while chloro and substituted triphenylphosphine are present at the remaining two positions. The anticancer activity of both complexes against five different cancer cell lines (LU – human lung carcinoma, established at UIC, Department of Surgical Oncology; MCF7 – human breast adenocarcinoma, ATCC number HTB‐22?; MDA‐MB‐231 – human breast adenocarcinoma, ATCC number HTB‐26?; Hepa‐1c1c7 – mouse liver hepatoma, ATCC number CRL‐2026?; PC‐3 – human prostate adenocarcinoma, ATCC number CRL‐1435?) was determined by MTT assay, revealing 2 has higher activity than 1 . A drug–calf thymus DNA binding study with UV–visible spectroscopy reveals a higher DNA binding affinity of 2 (3.511 × 10⁴ M^?1) than 1 (4.213 × 10³ M^?1). Density functional theory studies confirm the relatively more stable nature of 2 than 1 . Copyright © 2016 John Wiley & Sons, Ltd.     

Synthesis,crystal structure,and in vitro antitumor activities of copper(II) complexes containing tetradentate pyridine-based ligands

Several new Cu(II) complexes of Schiff bases obtained by condensation of 2-[N-(α-picolyl)-amino]-benzophenone with different chiral amino acids were synthesized and characterized by physico-chemical and spectroscopic methods. The crystal structure of one of the complexes was determined using single crystal X-ray diffraction. The ligands were coordinated to the metal atom in a tetradentate manner with ONNN donor sets using the carboxyl oxygen, azomethine nitrogen, CON⁻, and pyridine nitrogen. The cytotoxicities of the complexes were evaluated against human cancer cells. The substituents on the aromatic rings strongly influenced the cytotoxicities of the complexes. The complex with bromine substituents on the pyridine rings showed the highest cytotoxicity. The antitumor activities against tumor cell lines were assayed in vitro, and the complexes were found to be highly effective, with six of the nine complexes having inhibition ratios better than that of 5-Fluorouracil. This behavior is indicative of a high ability to circumvent the cellular drug resistance mechanisms.     

2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma,human lung and breast cancer cell lines

Indole derivatives have attractive anticancer properties and may be a future hope for better anticancer drug(s) of low toxicity and high potency. In this paper, syntheses of 2-phenylindole derivatives have been described via Fischer indole synthesis through a one-pot solvent-free method. The synthesized compounds were screened for anticancer potential in vitro against murine melanoma (B16F10), human lung cancer (A549), and human breast cancer (MDA-MB-231) cell lines. The results highlighted that 2-phenylindole derivatives are also promising anticancer agents in case of melanoma and lung cancer along with the breast cancer. Molecular docking analyses with possible targets for melanoma (NEDD4-1) and lung cancer (EGFR) were also performed to understand specific interactions of 2-phenylindole derivatives with the amino acid residues of the receptors.     

Synthesis, crystal structure, and in vitro antitumor activity of a novel tetranuclear Di-n-butyltin(IV)

A di-n-butyltin(IV) complex with (E)-3-(4-(9H-carbazole-9-yl)phenyl) acrylic acid (HL) of the formula {[n-Bu₂SnOL]₂O}₂ was synthesized and characterized by X-ray crystallography. This complex is a tetranuclear one with ladder framework. Furthermore, this complex was tested in vitro for its cytotoxic activity, using human hepatocellular carcinoma cell line (BEL-7402) and human hepatocellular liver carcinoma cell line (HepG2); 5-Fluorouracil was used as a positive control substance. This complex showed cytotoxicity greater than that of 5-Fluorouracil.     

In vitro and in vivo antitumor activity of Scutellaria barbate extract on murine liver cancer

In the present study, we investigated the in vitro and in vivo antitumor effects of crude extract of Scutellaria Barbate (CE-SB) on mouse hepatoma H22 cells. The MTT assay was used to determine the growth inhibition of H22 cells in vitro. The in vivo therapeutic effects of CE-SB were determined using H22 tumor bearing mice. Besides, the body weight, tumor weight, thymus index and spleen index of H22 bearing mice were also measured. The tumor inhibitory rate (IR) was calculated according to the mean weight of tumor (MWT). The phagocytotic function of macrophages was examined by observing peritoneal macrophages phagocytize chicken RBC. The results showed that CE-SB could inhibit the growth of hepatoma H22 Cells in vitro and in vivo. Furthermore, CE-SB could improve immune function of H22 tumor bearing mice. Together these results indicate that CE-SB has antitumor activity and seems to be safe and effective for the use of anti-tumor therapy.     

Polyoxometalates functionalized by bisphosphonate ligands: synthesis, structural, magnetic, and spectroscopic characterizations and activity on tumor cell lines

We report the synthesis and characterization of eight new Mo, W, or V-containing polyoxometalate (POM) bisphosphonate complexes with metal nuclearities ranging from 1 to 6. The compounds were synthesized in water by treating Mo(VI), W(VI), V(IV), or V(V) precursors with biologically active bisphosphonates H(2)O(3)PC(R)(OH)PO(3)H(2) (R = C(3)H(6)NH(2), Ale; R = CH(2)S(CH(3))(2), Sul and R = C(4)H(5)N(2), Zol, where Ale = alendronate, Sul = (2-Hydroxy-2,2-bis-phosphono-ethyl)-dimethyl-sulfonium and Zol = zoledronate). Mo(6)(Sul)(2) and Mo(6)(Zol)(2) contain two trinuclear Mo(VI) cores which can rotate around a central oxo group while Mo(Ale)(2) and W(Ale)(2) are mononuclear species. In V(5)(Ale)(2) and V(5)(Zol)(2) a central V(IV) ion is surrounded by two V(V) dimers bound to bisphosphonate ligands. V(6)(Ale)(4) can be viewed as the condensation of one V(5)(Ale)(2) with one additional V(IV) ion and two Ale ligands, while V(3)(Zol)(3) is a triangular V(IV) POM. These new POM bisphosphonates complexes were all characterized by single-crystal X-ray diffraction. The stability of the Mo and W POMs was studied by (31)P NMR spectroscopy and showed that all compounds except the mononuclear Mo(Ale)(2) and W(Ale)(2) were stable in solution. EPR measurements performed on the vanadium derivatives confirmed the oxidation state of the V ions and evidenced their stability in aqueous solution. Electrochemical studies on V(5)(Ale)(2) and V(5)(Zol)(2) showed reduction of V(V) to V(IV), and magnetic susceptibility investigations on V(3)(Zol)(3) enabled a detailed analysis of the magnetic interactions. The presence of zoledronate or vanadium correlated with the most potent activity (IC(50)~1-5 μM) against three human tumor cell lines.