Hydrogen-bond-driven supramolecular helical assembly of a coumarin-substituted phthalonitrile derivative: synthesis and in vitro anticancer activity against colorectal adenocarcinoma.

Phthalonitrile derivatives are generally reported to crystallize in space groups P21/c and P1 in the literature. In this study, 7-hydroxy-4,8-dimethyl-3-pentylcoumarin (2) and its phthalonitrile derivative (2d) were crystallized; 2d crystallized in the rare trigonal space group R3. In the phthalonitrile derivative (2d), weak C-H...O hydrogen-bonding interactions promoted the formation of supramolecular double helices, and these supramolecular P and M double helices came together to form a honeycomb-like architectural motif involving one-dimensional tubular channels. In silico molecular-docking studies were performed to support the experimental processes and the results agree with each other. In vitro studies of compounds 2 and 2d were performed in LoVo colorectal adenocarcinoma and CCD18Co healthy human cell lines using flow cytometry. For compounds 2 and 2d, there was a statistically significant increase (p < 0.001) in both early and late apoptosis with respect to the control in a dose-dependent manner.

(E)-1-(4-Hydroxyphenyl)-3-(substituted-phenyl)prop-2-en-1-ones: Synthesis, In Vitro Cytotoxic Activity and Molecular Docking Studies.

A series of chalcone compounds (2-11) were designed and synthesized to determine their cytotoxic effects. The structures of 2-11 were fully characterized by their physical and spectral data. The in vitro cytotoxic effects of 2-11 were evaluated against human ovarian cancer (A2780), breast cancer (MCF-7) and prostate cancer (PC-3 and LNCaP) cell lines. The activity potentials of compounds were further evaluated through molecular docking studies with AutoDock4 and Vina softwares. All the compounds (except compound 5) showed significant cytotoxic effects at high doses in all cancer cell lines. Among all the compounds studied, one compound i.e. compound 2 demonstrated dose-dependent activity, particularly against A2780/LNCaP cancer cell lines. The most effective compounds 8, 9, 10 and 11 reduced the cell viability of A2780, MCF-7, PC-3 and LNCaP cells by 50-98%, while other compounds 2, 4 and 7 reduced the cell viability of A2780 cells by 70-90% at concentrations of 50 and 100 µM.

Synthesis of New Cinnamoyl-Amino Acid Conjugates and in Vitro Cytotoxicity and Genotoxicity Studies.

Amino acid conjugates are described by the reaction of amino acids with bioactive organic groups such as vitamins, hormones, flavonoids, steroids, and sugars. In this study, 12 new conjugates were synthesized by reaction of cinnamic acid derivatives with various amino acids. Cytotoxic studies against four different human cancer cells (MCF7, PC-3, Caco-2, and A2780) were carried out by MTT assay method at five different concentrations. The structure-activity relationships based on the cell viability rates were evaluated. To compare the anticancer activities of the compounds using computational chemistry methods, they were docked against A2780 human ovarian cancer, Michigan Cancer Foundation-7 (MCF7), human prostate cancer (PC-3) and human colon epidermal adenocarcinoma (Caco-2) cell lines and compared with the standard 5-Fluorouracil. The results indicate that the efficacy of cinnamic acid derivatives increases with the presence of amino acids. Comet assay was conducted to understand whether the cell deaths occur through DNA damage mechanism and the results exhibit that the changes in the specified parameters were statistically significant (p<0.05). Our study demonstrated that the compounds cause cell death through the formation of DNA damage mechanism.

Synthesis and spectroscopic characterizations of hexakis[(1-(4'-oxyphenyl)-3-(substituted-phenyl)prop-2-en-1-one)]cyclotriphosphazenes: their in vitro cytotoxic activity, theoretical analysis and molecular docking studies.

The hexachlorocyclotriphosphaze compound (N3P3Cl6, HCCP) was reacted with excess (E)-(1-(4'-oxyphenyl)-3-(substituted-phenyl)prop-2-en-1-ones (2-11) to produce hexakis[(1-(4-oxyphenyl)-3-(substituted-phenyl)prop-2-en-1-one)]cyclotriphosphazenes (CP 2-11). The structures of products (CP 2-11) were confirmed using elemental analysis, FT-IR, MS spectral analysis as well as 31P, 1H and 13C-APT NMR techniques and their thermal properties determined by TGA and DSC techniques. The HOMO-LUMO energy gap and chemical reactivity identifiers were calculated and HOMO and LUMO images were viewed. According to the calculations, all the chemical potential values of CP 2-11 are negative and it shown that the molecules are stable. The in vitro cytotoxic of CP 2-11 investigated and their activity potentials were evaluated by molecular docking studies with Autodock Vina softwares. CP 2-11 compounds were found to demonstrate cytotoxic activity against human cancer cell lines (A2780, LNCaP and PC-3). The CP 2-11 compounds reduced the cell viability against all cancer cell lines in the range 36%-90% especially. The results showed that these compounds are powerful candidate molecules for pharmaceutical applications.

Fluorescence "Turn On-Off" Sensing of Copper (II) Ions Utilizing Coumarin-Based Chemosensor: Experimental Study, Theoretical Calculation, Mineral and Drinking Water Analysis.

Herein, we report the preparation of a fluorescent sensor based on coumarin derivative for copper (II) ion sensing in CH3CN/HEPES media. 6,7-dihydroxy-3-(4-(trifluoro)methylphenyl)coumarin (HMAC) sensor was fabricated and analyzed by spectroscopic techniques. The sensor demonstrates "turn on-off" fluorescence quenching in the presence of copper (II) ions at 458 nm. A clear complex between the chemosensor HMAC and copper (II) ions was characterized by ESI-MS as well as the Job's method. Also, the limit of detection (LOD, 3σ/k) value was determined as 24.5 nM in CH3CN/HEPES (95/5, v/v) buffer media (pH = 7.0). This value is lower than the admissible level of copper (II) ions in drinking water (maximum 31.5 µM) reported by EU Water Framework Directive (WFD) and World Health Organization (WHO) guidelines. The theoretical calculations (density functional theory, DFT) have been performed for the geometric optimized structures. As a final stage, real sample analyses have successfully been performed by using HMAC, as well as ICP-OES method. The relative standard deviation for copper (II) in mineral and drinking water samples has been determined to be below 0.15% and recovery values are in the range of 95.48-109.20%.

Fluorescent sensing platform for low-cost detection of Cu2+ by coumarin derivative: DFT calculation and practical application in herbal and black tea samples.

A fluorogenic probe based on a coumarin-derivative for Cu2+ sensing in CH3CN/H2O media (v/v, 95/5, 5.0 µM) was developed and applied in real samples. 3-(4-chlorophenyl)-6,7-dihydroxy-coumarin (MCPC) probe was obtained by synthetic methodologies and identified by spectral techniques. The probe MCPC showed remarkable changes with a "turn-off" fluorogenic sensing approach for the monitoring of Cu2+ at 456 nm under an excitation wavelength of 366 nm. The response time of the probe MCPC was founded as only 1 min. The detection limit of the probe MCPC was recorded to be 1.47 nM. The binding constant and possible stoichiometric ratio (1:1) values were determined by Benesi-Hildebrand and Job's plot systems, respectively. The mechanism of the probe MCPC with Cu2+ was further confirmed by ESI-MS and FT-IR analyses, as well as supported by theoretical calculations. Furthermore, the probe MCPC was successfully employed for the practical applications to sense Cu2+ in different herbal and black tea samples. The proposed sensing method was also verified by ICP-OES method.

Selective and sensitive fluorescent and colorimetric chemosensor for detection of CO32- anions in aqueous solution and living cells.

A new colorimetric and fluorescent chemosensor for visual determination of carbonate ions was developed by the microwave assisted solvent free synthesis of 7,8-dihydroxy-3-(4-methylphenyl) coumarin (DHMC). The structural characterization of DHMC was confirmed by microanalysis and spectroscopy methods (MALDI-TOF, FT-IR, 1H NMR, 13C NMR, and 2D HETCOR). The binding behaviors of DHMC were investigated towards various anions by UV-vis and fluorescence spectroscopy. DHMC showed a selective and sensitive fluorometric and colorimetric responses towards carbonate ion over other anions. The detection limit of CO32- was found to be 1.03 µM. Moreover, the fluorescence imaging in living cells suggests that DHMC has a great potential in the biological imaging application. It has been demonstrated that DHMC can be used as a rapid and reliable sensor for the determination of carbonate anion in a variety of practical applications.

Geraniol attenuates hydrogen peroxide-induced liver fatty acid alterations in male rats.

BACKGROUND: Hydrogen peroxide (H2O2) is an oxidant agent and this molecule naturally occurs in the body as a product of aerobic metabolism. Geraniol is a plant-derived natural antioxidant. The aim of this study was to determine the role of geraniol on hepatic fatty acids alterations following H2O2-induced oxidative stress in male rats. METHODS: After randomization, male Wistar rats were divided into four groups (n = 7 each group). Geraniol (50 mg/kg, dissolved in corn oil) and H2O2 (16 mg/kg, dissolved in distilled water) were administered by an intraperitoneal injection. Administrations were performed during 30 days with 1-day interval. RESULTS: Administration of H2O2 resulted with a significant increase in malondialdehyde (MDA) and a significant decrease in glutathione (GSH) peroxidase glutathione level; geraniol restored its effects on liver. However, hepatic catalase (CAT) activities were significantly higher in H2O2, geraniol, and geraniol+H2O2 groups than control group. The ratio of hepatic total saturated fatty acids increased in H2O2-treated animals compared with control. In addition, hepatic total unsaturated fatty acids reduced in H2O2 group compared with control. The percentages of both hepatic total saturated and unsaturated fatty acids were not different between geraniol+H2O2 and control groups. CONCLUSIONS: H2O2-induced oxidative stress may affect fatty acid composition in liver and body. Geraniol can partly restore oxidative hepatic damage because it cannot completely reverse the H2O2-induced increase in hepatic CAT activities. Moreover, this natural compound can regulate hepatic total saturated and unsaturated fatty acids percentages against H2O2-induced alterations.

Coumarin Based Highly Selective "off-on-off" Type Novel Fluorescent Sensor for Cu2+ and S2- in Aqueous Solution.

Solvent free synthesis of 6,7-dihydroxy-3-(3-chlorophenyl) coumarin (CFHC) was designed and obtained by the interaction of 2-(2,4,5-trimethoxyphenyl)-1-(3-chlorophenyl)acrylonitrile with pyridinium hydrochloride in the presence of silica gel by using microwave irradiation. The characterization of CFHC was confirmed by FT-IR, 1H, 13C, 13C-APT and 2D HETCOR spectroscopy methods. The optical behavior of CFHC towards metal ions was investigated by UV-visible and fluorescence spectroscopy. CFHC showed "on-off" type fluorescence response towards Cu2+ with high selectivity in aqueous solution (CH3CN/H2O, 9/1, v/v). Once binding with Cu2+, CFHC-Cu2+ complex also displayed high selectivity for sulfide, resulting in "off-on" type sensing of sulfide anion. Graphical abstract Visual fluorescence changes upon addition of various metal ions (5.0 eq.) to CFHC in CH3CN/H2O (90:10, v/v) under UV excitation (365 nm).

Synthesis, characterization, and biological-pharmacological evaluation of new phosphazenes bearing dioxybiphenyl and schiff base groups.

A new spirocyclophosphazene, 2,2-bis(2-formylphenoxy)-4,4,6,6-bis[spiro(2',2″-dioxy-1'-1″-biphenylyl)]cyclotriphosphazene (3), was obtained from the reaction of 2,2-dichloro-4,4,6,6-bis[spiro(2',2″-dioxy-1'-1″-biphenylyl)]cyclotriphosphazene (2) with 2-hydroxybenzaldehyde. New phosphazene derivatives bearing Schiff base and dioxybiphenyl groups have been synthesized by the reactions of 3 with different amines. The structures of the compounds were defined by elemental analysis, IR, (1) H, (13) C, and (31) P NMR spectroscopy. All the synthesized compounds were screened for their antibacterial activity against both types of Gram-negative and Gram-positive bacteria. The most potent antibacterial compound of this series was compound 12 which has the low MIC value of 3.75-0.9375 µg/mL. Both minimal inhibitory concentrations (MIC) and inhibition zones were determined in order to monitor the efficacy of the synthesized compounds. New compounds were also screened for anticonvulsant, CNS depressant, and sedative-hypnotic activity. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight phosphazenes were examined in the maximal electroshock-induced seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. Compounds 4, 5, and 11 were found to be active in both MES screen and scPTZ screen at 0.5 h. All except 12 showed more than 44% decrease in locomotor activity after 1 h of compound administration via actophotometer screen. CNS-depressant activity screened with the help of the forced swim method resulted in some potent compounds. Except for 7 and 12 other tested compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time.

4-{4-[(E)-(2-Hy-droxy-phen-yl)imino-methyl]phen-oxy}benzene-1,2-di-carbo-nitrile.

The asymmetric unit of the title compound, C(21)H(13)N(3)O(2), contains two independent mol-ecules with a similar structure. In one mol-ecule, the central benzene ring is oriented with respect to the terminal benzene rings at 27.23 (7) and 67.96 (7)°; in the other mol-ecule, the corresponding dihedral angles are 12.42 (7) and 64.55 (7)°. In both molecules, there is a short O-H⋯N interaction involving the OH group and the adjacent N atom. In the crystal, there are O-H⋯N hydrogen bonds, and C-H⋯O and N-H⋯O interactions linking the molecules to form a three-dimensional network. π-π stacking between the pyridine and benzene rings and between the benzene rings [centroid-centroid distances = 3.989 (2), 3.705 (2) and 3.607 (2) Å] may further stabilize the structure. A weak C-H⋯π inter-action is present in the crystal.

4-(Furan-2-ylmeth-oxy)benzene-1,2-dicarbonitrile.

In the title compound, C(13)H(8)N(2)O(2), prepared from furfuryl alcohol and 4-nitro-phthalonitrile in the presence of potassium carbonate in dimethyl-formamide, the furan and benzene rings are oriented at a dihedral angle of 53.45 (9)°. In the crystal, weak C-H⋯O and C-H⋯N hydrogen bonds link the mol-ecules into a three-dimensional network.

A kinetic study of mercury(II) transport through a membrane assisted by new transport reagent.

BACKGROUND: A new organodithiophosphorus derivative, namely O-(1,3-Bispiperidino-2-propyl)-4-methoxy phenyldithiophosphonate, was synthesized and then the kinetic behavior of the transport process as a function of concentration, temperature, stirring rate and solvents was investigated. RESULTS: The compound 1 was characterized by elemental analysis, IR, 1H and 31P NMR spectroscopies. The transport of mercury(II) ion by a zwitterionic dithiophosphonate 1 in the liquid membrane was studied and the kinetic behavior of the transport process as a function of concentration, temperature, stirring rate and solvents was investigated. The compound 1 is expected to serve as a model liquid membrane transport with mercury(II) ions. CONCLUSION: A kinetic study of mercury(II) transport through a membrane assisted by O-(1,3-Bispiperidino-2-propyl)-4-methoxy phenyldithiophosphonate was performed. It can be concluded that the compound 1 can be provided a general and straightforward route to remove toxic metals ions such as mercury(II) ion from water or other solution.