Studies on the Red Sea Sponge Haliclona sp. for its Chemical and Cytotoxic Properties.

BACKGROUND: A great number of novel compounds with rich chemical diversity and significant bioactivity have been reported from Red Sea sponges. OBJECTIVE: To isolate, identify, and evaluate the cytotoxic activity of the chemical constituents of a sponge belonging to genus Haliclona collected from the Eastern coast of the Red Sea. MATERIALS AND METHODS: The total ethanolic extract of the titled sponge was subjected to intensive chromatographic fractionation and purification guided by cytotoxic bioassay toward various cancer cell lines. The structures of the isolated compounds were elucidated using spectroscopic techniques including one-dimension and two-dimension nuclear magnetic resonance, mass spectrometry, ultraviolet, and infrared data, as well as comparison with the reported spectral data for the known compounds. X-ray single-crystal structure determination was performed to determine the absolute configuration of compound 4. The screening of antiproliferative activity of the compounds was carried on three tumor cell lines, namely the human cervical cancer (HeLa), human hepatocellular carcinoma (HepG2), and human medulloblastoma (Daoy) cells using MTT assay. RESULTS: This investigation resulted in the isolation of a new indole alkaloid, 1-(1H-indol-3-yloxy) propan-2-ol (1), with the previously synthesized pyrrolidine alkaloid, (2R, 3S, 4R, 5R) pyrrolidine-(1-hydroxyethyl)-3,4-diol hydrochloride (4), isolated here from a natural source for the first time. In addition, six known compounds tetillapyrone (2), nortetillapyrone (3), 2-methyl maleimide-5-oxime (5), maleimide-5-oxime (6), 5-(hydroxymethyl) dihydrofuran-2 (3H)-one (7), and ergosta-5,24 (28)-dien-3-ol (8) were also identified. Most of the isolated compounds exhibited weak cytotoxic activity against HepG-2, Daoy, and HeLa cancer cell lines. CONCLUSION: This is the first report of the occurrence of the indole and pyrrolidine alkaloids, 1-(1H-indol-2-yloxy) propan-2-ol (1), and the - (1-hydroxyethyl)-3,4-diol hydrochloride (4), in the Red Sea Haliclona sp. SUMMARY: From the Red Sea Haliclona sp. two alkaloids with indole and pyrrolidine nuclei, 1-(1H-indol-2-yloxy) propan-2-ol-(1) and pyrrolidine-(1-hydroxyethyl)-3,4-diol hydrochloride (4) were isolated and fully characterized; in addition to six known compounds (2, 3, 5-8)The absolute configuration and the three-dimension stereo-molecular structure of compound 4 were determined by X-ray crystallographyThe different extracts and isolated compounds showed weak cytotoxic activity against HepG-2, Daoy, and HeLa cancer cell lines.

Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives.

We describe here the synthesis of dihydropyrimidines derivatives 3a-p, and evaluation of their α-glucosidase enzyme inhibition activities. Compounds 3b (IC50=62.4±1.5 µM), 3c (IC50=25.3±1.26 µM), 3d (IC50=12.4±0.15 µM), 3e (IC50=22.9±0.25 µM), 3g (IC50=23.8±0.17 µM), 3h (IC50=163.3±5.1 µM), 3i (IC50=30.6±0.6 µM), 3m (IC50=26.4±0.34 µM), and 3o (IC50=136.1±6.63 µM) were found to be potent α-glucosidase inhibitors in comparison to the standard drug acarbose (IC50=840±1.73 µM). The compounds were also evaluated for their in vitro cytotoxic activity against PC-3, HeLa, and MCF-3 cancer cell lines, and 3T3 mouse fibroblast cell line. All compounds were found to be non cytotoxic, except compounds 3f and 3m (IC50=17.79±0.66-20.44±0.30 µM), which showed a weak cytotoxic activity against the HeLa, and 3T3 cell lines. In molecular docking simulation study, all the compounds were docked into the active site of the predicted homology model of α-glucosidase enzyme. From the docking result, it was observed that most of the synthesized compounds showed interaction through carbonyl oxygen atom and polar phenyl ring with active site residues of the enzyme.

2-((Benzimidazol-2-yl)thio)-1-arylethan-1-ones: Synthesis, crystal study and cancer stem cells CD133 targeting potential.

In order to develop a potent anti-tumor agent that can target both cancer stem cells and the bulk of tumor cells, a series of 2-((benzimidazol-2-yl)thio)-1-arylethan-1-ones 5a-o was synthesized. All compounds were evaluated for their anti-proliferative activity towards colon HT-29 cancer cell line. In addition, their inhibitory effect against cell surface expression of CD133, a potent cancer stem cells (CSCs) marker, in the same cells was evaluated by flow cytometry at 10 µM. Compound 5l emerged as the most active anti-proliferative analog against HT-29 (IC50 = 18.83 ± 1.37 µM), that almost equipotent as 5-fluorouracil (IC50 = 15.83 ± 1.63 µM) with 50.11 ± 4.05% inhibition effect on CD133 expression, suggested dual targeted effect. Also, compounds 5h, 5j, 5k and 5m-o inhibited the expression of CD133 with more than 50%. The SAR study pointed out the significance of substitution of the pendent phenyl group with lipophilic electron-donating groups or replacing it by 2-thienyl or 2-furyl groups.

Synthesis, Characterization, and Anti-Cancer Activity of Some New N'-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones Derivatives.

Eight novel N'-(2-oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazone derivatives 4a-h were synthesized and fully characterized by IR, NMR ((1)H-NMR and (13)C-NMR), elemental analysis, and X-ray crystallography. The cyto-toxicity and in vitro anti-cancer evaluation of the prepared compounds have been assessed against two different human tumour cell lines including human liver (HepG2) and leukaemia (Jurkat), as well as in normal cell lines derived from human embryonic kidney (HEK293) using MTT assay. The compounds 3e, 3f, 4a, 4c, and 4e revealed promising anti-cancer activities in tested human tumour cells lines (IC50 values between 3 and 7 µM) as compared to the known anti-cancer drug 5-Fluorouracil (IC50 32-50 µM). Among the tested compounds, 4a showed specificity against leukaemia (Jurkat) cells, with an IC50 value of 3.14 µM, but this compound was inactive in liver cancer and normal cell lines.

Structural and spectral investigations of the recently synthesized chalcone (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one, a potential chemotherapeutic agent.

BACKGROUND: Chalcones (1,3-diaryl-2-propen-1-ones, represent an important subgroup of the polyphenolic family, which have shown a wide spectrum of medical and industrial application. Due to their redundancy in plants and ease of preparation, this category of molecules has inspired considerable attention for potential therapeutic uses. They are also effective in vivo as anti-tumor promoting, cell proliferating inhibitors and chemo preventing agents. RESULTS: Synthesis and molecular structure investigation of (E)-3-mesityl-1-(naphthalen-2-yl) prop-2-en-1-one (3) is reported. The structure of the title compound 3 is confirmed by X-ray crystallography. The optimized molecular structure of the studied compound is calculated using DFT B3LYP/6-311G (d,p) method. The calculated geometric parameters are in good agreement with the experimental data obtained from our reported X-ay structure. The calculated IR fundamental bands were assigned and compared with the experimental data. The electronic spectra of the studied compound have been calculated using the time dependant density functional theory (TD-DFT). The longest wavelength band is due to H → L (79 %) electronic transition which belongs to π-π* excitation. The (1)H- and (13)C-NMR chemical shifts were calculated using gauge independent atomic orbitals (GIAO) method, which showed good correlations with the experimental data (R(2) = 0.9911-0.9965). The natural bond orbital (NBO) calculations were performed to predict the natural atomic charges at different atomic sites. The molecular electrostatic potential (MEP) was used to visualize the charge distribution on the molecule. Molecular docking results suggest that the compound might exhibit inhibitory activity against GPb and may act as potential anti-diabetic compound. CONCLUSIONS: (E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one single crystal is grown and characterized by single crystal X-ray diffraction, FT-IR, UV-vis, DFT and optimized geometrical parameters are close to the experimental bond lengths and angles. Molecular stability was successfully analyzed using NBO and electron delocalization is confirmed by MEP. Prediction of Activity Spectra Analysis of the title compound, predicts anti-diabetic activity with probability to have an active value of 0.348. Graphical Abstract(E)-3-Mesityl-1-(naphthalen-2-yl) prop-2-en-1-one: a crystal structure and computational studies.

Nickel-catalyzed and benzoic acid-promoted direct sulfenylation of unactivated arenes.

A nickel-catalyzed and benzoic acid-promoted direct sulfenylation of unactivated arenes using removable 2-(pyridine-2-yl)-isopropylamine as a directing group is described. This strategy provides an efficient access to valuable aryl sulfides with ample substrate scope and a high degree of functional group tolerance.

Preparation of Multifunctional Nanoprobes for Tumor-Targeted Fluorescent Imaging and Therapy.

Nanoparticles are emerging as versatile nanoplatforms for the construction of multifunctional nanoprobes, which not only can deliver drugs into desired tumor regions but also are able to monitor the delivery, release and biodistribution of drugs in real time. In order to assist drug delivery, fluorescent imaging that can make the transportation viewable is often used. Then, various fluorescent nanoprobes that are composed of fluorescent or non-fluorescent nanocarrier, small-molecular fluorophore, drug, targeting ligand are developed and applied in biomedical applications. In this review paper, we will summarize chemical strategies for the construction of multifunctional nanoprobes and for controlled release of drugs. Then, recent examples on fluorescent nanoprobes, which are based on quantum dots, carbon nanodots, upconversion nanoparticles and other nanomaterials, and their applications in optical-guided drug delivery will be reviewed.

Targeting HER-2 over expressed breast cancer cells with 2-cyclohexyl-N-[(Z)-(substituted phenyl/furan-2-yl/thiophene-2-yl)methylidene]hydrazinecarbothioamide.

Cyclohexyl thiosemicarbazone derivatives (C1-14) were synthesized, characterized and evaluated against HER-2 over expressed breast cancer cells. The synthesized compounds were screened in vitro against four breast cancer cell lines; SKBr-3, MCF-7, MDA-MB-468 and MDA-MB-231. All the compounds showed activity against HER-2 over expressed SKBr-3 cells with (IC50 = 25.6 ± 0.07 µM-61.6 ± 0.4 µM). The most active compounds inhibit ALDH⁺ breast cancer stem cells more effectively than the cancer stem cells specific agent Salinomycin. Immunohistochemistry staining also confirmed that these compounds inhibit the expression of HER-2 on SKBr-3 cells. Compound C2 significantly inhibited the cell migration and cell adhesion of breast cancer cell lines. Compound C2 was found to most active compound of this series targeting HER-2 over expressed breast cancer cells.

Crystal structure of bis-{2-[(E)-(4-fluoro-benz-yl)imino-meth-yl]phenolato-κ(2) N,O}nickel(II).

The asymmetric unit of the title complex, [Ni(C14H11FNO)2], contains one-half of the mol-ecule with the Ni(II) cation lying on an inversion centre coordinated by a bidentate Schiff base anion. The cationic Ni(II) center is in a distorted square-planar coordination environment chelated by the imine N and phenolate O donor atoms of the two Schiff base ligands. The N and O donor atoms of the two ligands are mutually trans with Ni-N and Ni-O bond lengths of 1.9242 (10) and 1.8336 (9) Å, respectively. The fluoro-phenyl ring is almost orthogonal to the coordination plane and makes a dihedral angle of 82.98 (7)° with the phenolate ring. In the crystal, mol-ecules are linked into screw chains by weak C-H⋯F hydrogen bonds. Additional C-H⋯π contacts arrange the mol-ecules into sheets parallel to the ac plane.

Crystal structure of bis-{2-[(E)-(4-meth-oxy-lbenz-yl)imino-meth-yl]phenolato-κ(2) N,O (1)}nickel(II).

The asymmetric unit of the title compound, [Ni(C15H14NO2)2], comprises an Ni(II) cation, lying on an inversion centre, and a Schiff base anion that acts as a bidentate ligand. The Ni(II) cation is in a square-planar coordination environment binding to the imine N and phenolate O atoms of the two Schiff base ligands. The N- and O-donor atoms of the two ligands are mutually trans, with Ni-N and Ni-O bond lengths of 1.9191 (11) and 1.8407 (9) Å, respectively. The plane of the meth-oxy-benzene ring makes a dihedral angle of 84.92 (6)° with that of the phenolate ring. In the crystal, mol-ecules are linked into screw chains by weak C-H⋯O hydrogen bonds. Additional C-H⋯O hydrogen bonds, together with C-H⋯π contacts, arrange the mol-ecules into sheets parallel to the ac plane.

Three types of cytotoxic natural caged-scaffolds: pure enantiomers or partial racemates.

Two rare new natural products, the neocaged-xanthone pruniflorone T (1) and the rearranged caged-xanthone pruniflorone U (3), and the known caged-xanthone cochinchinone C (2) were isolated from the roots of Cratoxylum formosum ssp. pruniflorum. The unique structures of 1-3 were determined by analysis of NMR and X-ray diffraction data. The X-ray data of 1-3 revealed that they all exist with both enantiomers in their crystal packing. Separation of 1-3 by chiral HPLC led to the isolation of three pairs of enantiomers, (-)-1/(+)-1, (-)-2/(+)-2, and (-)-3/(+)-3, and their absolute configurations were determined by analysis of single-crystal X-ray diffraction and ECD spectroscopic data. A 1:1 mixture of 1 and 3 showed potent in vitro cytotoxicity against an MCF-7 human breast cancer cell line with an IC50 value of 0.11 µg/mL.

2,2'-[2,4-Bis(naphthalen-1-yl)cyclo-butane-1,3-di-yl]bis-(1-methyl-pyridinium) bis-(4-chloro-benzene-sulfonate): thermal-induced [2 + 2] cyclo-addition reaction of a heterostilbene.

The asymmetric unit of the title salt, C36H32N2 (2+)·2C6H4ClO3S(-), consists of one anion and one half-cation, the other half being generated by inversion symmetry. The dihedral angle between the pyridinium ring and the napthalene ring system in the asymmetric unit is 42.86 (6)°. In the crystal, cations and anions are linked by weak C-H⋯O inter-actions into chains along [010]. Adjacent chains are further arranged in an anti-parallel manner into sheets parallel to the bc plane. π-π inter-actions are observed involving the cations, with centroid-centroid distances of 3.7664 (8) and 3.8553 (8) Å.

(E)-2-[4-(Di-ethyl-amino)-styr-yl]-1-methyl-quinolin-1-ium 4-chloro-benzene-sulfonate monohydrate.

The asymmetric unit of the title hydrated salt, C22H25N2 (+)·C6H4ClO3S(-)·H2O, comprises two 2-[4-(di-ethyl-amino)-styr-yl]-1-methyl-quinolin-1-ium cations, two 4-chloro-benzene-sul-fon-ate anions and two solvent water mol-ecules. One ethyl group of both cations displays disorder over two positions in a 0.659 (2):0.341 (2) ratio in one mol-ecule and in a 0.501 (2):0.499 (2) ratio in the other. The sulfonate group of one anion is also disordered over two positions in a 0.893 (7):0.107 (7) ratio. The dihedral angle between the mean plane of the quinolinium ring system and that of benzene ring is 10.57 (18)° in one cation and 14.4 (2)° in the other. In the crystal, cations, anions and water mol-ecules are linked into chains along the [010] direction by O-H⋯Osulfonate hydrogen bonds, together with weak C-H⋯Osulfonate and C-H⋯Cl inter-actions. The cations are stacked by π-π inter-actions, with centroid-centroid distances in the range 3.675 (2)-4.162 (3) Å.

2-[(E)-2-(4-Eth-oxy-phen-yl)ethen-yl]-1-methyl-quinolinium 4-fluoro-benzene-sulfonate.

In the structure of the title salt, C20H20NO(+)·C6H4FO3S(-), the 4-(eth-oxy-phen-yl)ethenyl unit is disordered over two positions with a refined site-occupancy ratio of 0.610 (6):0.390 (6). The cation is nearly planar, the dihedral angle between the quinolinium and benzene rings being 6.7 (4) and 1.7 (7)° for the major and minor components, respectively. The eth-oxy group is essentially coplanar with the benzene ring [C-O-C-Cmethy = 177.1 (8) and 177.8 (12)° for the major and minor components, respectively]. In the crystal, cations and anions are linked into chains along the b-axis direction by C-H⋯Osulfon-yl weak inter-actions. These chains are further connected into sheets parallel to (001) by C-H⋯Osulfon-yl weak inter-actions. The chains are also stacked along the a axis through π-π inter-actions involving the quinolinium and benzene rings [centroid-centroid distances = 3.636 (5) Šfor the major component and 3.800 (9) Šfor the minor component]. C-H⋯π inter-actions are also present.

Poly[µ5-(4-meth-oxy-benzene-sulfonato)-sodium].

In the title complex, [Na(C7H7O4S)] n , the Na(I) ion is coord-inated in a slightly distorted penta-gonal-bipyramidal environment by seven O atoms [Na-O = 2.3198 (16)-2.5585 (17) Å]. The 4-methoxybenzenesulfonate anions act as bis-chelating and bridging ligands, forming a two-dimensional polymer parallel to (001), which is further linked into a three-dimensional network by weak C-H⋯O hydrogen bonds.

(E)-2-[4-(Di-ethyl-amino)-styr-yl]-1-methyl-quinolinium 4-fluoro-benzene-sulfonate monohydrate.

In the title hydrated molecular salt, C22H25N2 (+)·C6H4FO3S(-)·H2O, the cation displays whole mol-ecule disorder over two sets of sites in a 0.780 (5):0.220 (5) ratio. The quinolinium ring system is essentially planar, with r.m.s. deviations of 0.0162 and 0.0381 Šfor the major and minor disorder components, respectively. The dihedral angles between the mean plane of the quinolinium ring system and the benzene ring are 5.1 (3) and 7.7 (11)°, respectively, for the major and minor components in the cation. In the crystal, cations, anions and water mol-ecules are linked into chains along [010] by O-H⋯O hydrogen bonds and are further connected into a three-dimensional network by weak C-H⋯O and C-H⋯F inter-actions. In addition, π-π inter-actions with centroid-centroid distances of 3.634 (3), 3.702 (5) and 3.838 (5) Šare observed.

New inhibitors of ROS generation and T-cell proliferation from Myrtus communis.

Phytochemical investigation on Myrtus communis Linn. afforded myrtucommuacetalone (1) with an unprecedented carbon skeleton and a new phloroglucinol-type compound, myrtucommulone M (2), along with four known constituents 3-6. Their structures were established by extensive analyses of NMR and mass spectral data as well as by single-crystal X-ray diffraction studies. These constituents were evaluated for their ability to modulate the immune response, based on their effects on various components of immune system. Compounds 1 and 5 exhibited significant inhibitory effect against nitric oxide (NO(•)) production. Compound 1 also exhibited significant antiproliferative activity (IC50 < 0.5 µg/mL) against T-cell proliferation. Myricetin (3) exerted a significant inhibition (IC50 = 1.6 µg/mL) on zymosan-stimulated whole blood phagocytes ROS production. Compounds 1 and 3 were active against PMA-stimulated ROS generation.

(2,2'-Bipyridine-κ(2) N,N')[bis-(diphenyl-thio-phosphino-yl)meth-yl]lithium(I) benzene monosolvate.

In the title benzene-solvated heteroleptic lithium complex, [Li(C25H21P2S2)(C10H8N2)]·C6H6, the Li(I) ion is four-coordinated in a distorted tetra-hedral geometry by two S atoms and two N atoms of the two chelating ligands, viz. bis-(diphenyl-thio-phosphino-yl)methyl and 2,2'-bipyridine. The 2,2'-bipyridine mol-ecule is slightly twisted with a dihedral angle between the pyridine rings of 7.35 (12)°. Intra-molecular C-H⋯S hydrogen bonds are present. In the crystal, mol-ecules are stacked along the c axis by π-π inter-actions, with centroid-centroid distances of 3.6021 (15) and 3.6401 (16) Å. The crystal structure also features weak C-H⋯π inter-actions.

1-Methyl-4-[(E)-2-(3-hy-droxy-4-meth-oxy-phen-yl)ethen-yl]pyridinium 4-bromo-benzene-sulfonate monohydrate.

In the title hydrated salt, C15H16NO2 (+)·C6H4BrO3S(-)·H2O, the cation exists in an E conformation with respect to the ethenyl bond and is almost planar, with a dihedral angle of 2.62 (12)° between the planes of the pyridinium and benzene rings. The meth-oxy substituent deviates slightly from the plane of its attached benzene ring [Cmeth-yl-O-C-C torsion angle = -11.6 (6)°]. In the crystal, the cations, anion and water mol-ecules are linked together into chains along [010] by O-H⋯O hydrogen bonds and weak C-H⋯O inter-actions. There is a short Br⋯O contact [3.029 (2) Å]. The crystal structure also features C-H⋯π inter-actions involving the benzene ring of the anion.

N-(4-Acetyl-phen-yl)-4-meth-oxy-benzene-sulfonamide.

The title compound, C15H15NO4S, was obtained by the condensation of 4-amino-aceto-phenone and 4-meth-oxy-benzene-sulfonyl chloride. The dihedral angle between the benzene rings is 86.56 (9)° and the mol-ecule has an approximate V-shaped conformation. The C atom of the meth-oxy group is roughly coplanar with its attached ring [deviation = 0.177 (3) Å], as is the methyl C atom of the acetyl group with its ring [deviation = 0.065 (2) Å]. An intra-molecular C-H⋯O inter-action generates an S(6) ring. In the crystal, N-H⋯O and C-H⋯O hydrogen bonds link the mol-ecules into [010] chains. Weak C-H⋯π inter-actions are also observed.