ABSTRACT
The crystal and mol-ecular structures of C14H12Cl2, (I), and C14H12Br2, (II), are described. The asymmetric unit of (I) comprises two independent mol-ecules, A and B, each disposed about a centre of inversion. Each mol-ecule approximates mirror symmetry [the Cb-Cb-Ce-Ce torsion angles = -83.46â (19) and 95.17â (17)° for A, and -83.7â (2) and 94.75â (19)° for B; b = benzene and e = ethyl-ene]. By contrast, the mol-ecule in (II) is twisted, as seen in the dihedral angle of 59.29â (11)° between the benzene rings cf. 0° in (I). The mol-ecular packing of (I) features benzene-C-Hâ¯π(benzene) and Clâ¯Cl contacts that lead to an open three-dimensional (3D) architecture that enables twofold 3D-3D inter-penetration. The presence of benzene-C-Hâ¯π(benzene) and Brâ¯Br contacts in the crystal of (II) consolidate the 3D architecture. The analysis of the calculated Hirshfeld surfaces confirm the influence of the benzene-C-Hâ¯π(benzene) and Xâ¯X contacts on the mol-ecular packing and show that, to a first approximation, Hâ¯H, Câ¯H/Hâ¯C and Câ¯X/Xâ¯C contacts dominate the packing, each contributing about 30% to the overall surface in each of (I) and (II). The analysis also clearly differentiates between the A and B mol-ecules of (I).
ABSTRACT
Three metal(II) complexes [CoLCl2], [CuLCl2] and [ZnL2Cl2] {Lâ¯=â¯2chloro3((3dimethylamino)propylamino)naphthalene1,4dione} have been synthesized and characterized using analytical, thermal and spectral techniques (FT-IR, UV-Vis, ESR and ESI-MS). The structure of the L has been confirmed by single crystal XRD study. The complexes show good binding propensity to bovine serum albumin (BSA) having relatively higher binding constant values (104â¯M-1) than the ligand. Fluorescence spectral studies indicate that [CoLCl2] binds relatively stronger with CT DNA through intercalative mode, exhibiting higher binding constant (2.22â¯×â¯105â¯M-1). Agarose gel electrophoresis run on plasmid DNA (pUC18) prove that all the complexes showed efficient DNA cleavage via hydroxyl radical mechanism. The complexes were identified as potent anticancer agents against two human cancer cell lines (MCF7 and A549) by comparing with cisplatin. Co(II) complex demonstrated greater cytotoxicity against MCF7 and A549 cells with IC50 values at 19 and 22⯵M, respectively.
Subject(s)
Coordination Complexes/chemistry , Macromolecular Substances/chemistry , Naphthoquinones/chemistry , A549 Cells , Animals , Cattle , Cell Death , Coordination Complexes/chemical synthesis , Crystallography, X-Ray , DNA/metabolism , DNA Cleavage , Electrons , Humans , Kinetics , Ligands , MCF-7 Cells , Molecular Docking Simulation , Protein Binding , Serum Albumin, Bovine/metabolismABSTRACT
Noncovalent carbon bonding, a recently explored σ-hole interaction, was hitherto supposed to be a weak and structure-guided interaction. Here, its role in the intramolecular stabilization of the cis conformation of the amide moiety in acylhydrazones is described. The calculations reveal an electron donation from the lone pair of the nitrogen atom to the empty antibonding C-N orbital [LP(N)âBD*(C-N)] with a concomitant stabilization energy of E(2) =1.2â kcal mol-1 .
ABSTRACT
The title compound, [Cd2(C8H8NS2)4], is a centrosymmetric dimer with both chelating and µ2-tridentate di-thio-carbamate ligands. The resulting S5 donor set defines a CdII coordination geometry inter-mediate between square-pyramidal and trigonal-bipyramidal, but tending towards the former. The packing features C-Hâ¯S and C-Hâ¯π inter-actions, which generate a three-dimensional network. The influence of these inter-actions, along with intra-dimer π-π inter-actions between chelate rings, has been investigated by an analysis of the Hirshfeld surface.
ABSTRACT
This study seeks to investigate the relationship between the structural modification and bioactivity of a series of tribenzyltin complexes with different ligands and substitutions. Complexation with the N,N-diisopropylcarbamothioylsulfanylacetate or isonicotinate ligands enhanced the anticancer properties of tribenzyltin compounds via delayed cancer cell-cycle progression, caspase-dependent apoptosis induction, and significant reduction in cell motility, migration and invasion. Halogenation of the benzyl ring improved the anticancer effects of the tribenzyltin compounds with the N,N-diisopropylcarbamothioylsulfanylacetate ligand. These compounds also demonstrated far greater anticancer effects and selectivity than cisplatin and doxorubicin, which provides a rationale for their further development as anticancer agents.
Subject(s)
Antineoplastic Agents/chemistry , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Cell Movement/drug effects , Neoplasm Invasiveness/prevention & control , Antineoplastic Agents/pharmacology , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Female , Humans , Ligands , Structure-Activity RelationshipABSTRACT
In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/ß-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.
Subject(s)
Antineoplastic Agents , Apoptosis/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Female , Humans , Neoplasm Proteins/metabolism , Neoplastic Stem Cells/pathologyABSTRACT
The YbIII atom in the title complex, [Yb(C27H24Cl3N4O3)] [systematic name: (2,2',2''-{(nitrilo)-tris-[ethane-2,1-di-yl(nitrilo)-methylyl-idene]}tris-(4-chloro-phenolato)ytterbium(III)], is coordinated by a trinegative, hepta-dentate ligand and exists within an N4O3 donor set, which defines a capped octa-hedral geometry whereby the amine N atom caps the triangular face defined by the three imine N atoms. The packing features supra-molecular layers that stack along the a axis, sustained by a combination of aryl-C-Hâ¯O, imine-C-Hâ¯O, methyl-ene-C-Hâ¯π(ar-yl) and end-on C-Clâ¯π(ar-yl) inter-actions. A Hirshfeld surface analysis points to the major contributions of Câ¯H/ Hâ¯C and Clâ¯H/Hâ¯Cl inter-actions (along with Hâ¯H) to the overall surface but the Clâ¯H contacts are at distances greater than the sum of their van der Waals radii.
ABSTRACT
In the solid state, the title compound, C12H16BrNO5 [systematic name: 4-bromo-2-((1E)-{[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminium-yl}meth-yl)-6-meth-oxy-benzen-1-olate], C12H16BrNO5, is found in the keto-amine tautomeric form, with an intra-molecular iminium-N-Hâ¯O(phenolate) hydrogen bond and an E conformation about the C=N bond. Both gauche (two) and anti relationships are found for the methyl-hydroxy groups. In the crystal, a supra-molecular layer in the bc plane is formed via hy-droxy-O-Hâ¯O(hy-droxy) and charge-assisted hy-droxy-O-Hâ¯O(phenolate) hydrogen-bonding inter-actions; various C-Hâ¯O inter-actions provide additional cohesion to the layers, which stack along the a axis with no directional inter-actions between them. A Hirshfeld surface analysis confirms the lack of specific inter-actions in the inter-layer region.
ABSTRACT
A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, (compound C1), was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50) value of 2.5±0.50 µg/mL after 48 hours treatment. The IC50 value was >30 µg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the present study obviously reveal potential cytotoxic effects of compound C1 against human breast cancer MCF-7 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Organotin Compounds/pharmacology , Schiff Bases/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Breast Neoplasms/metabolism , Cell Proliferation/drug effects , Cell Survival/drug effects , DNA Fragmentation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , L-Lactate Dehydrogenase/metabolism , MCF-7 Cells , Models, Molecular , Molecular Structure , Organotin Compounds/chemical synthesis , Organotin Compounds/chemistry , Reactive Oxygen Species/metabolism , Schiff Bases/chemical synthesis , Schiff Bases/chemistry , Structure-Activity RelationshipABSTRACT
Four new copper(II) complexes containing phosphonium substituted hydrazone (L) with the formulations [CuL]Cl(3), [Cu(phen)L]Cl(4), [Cu(bpy)L]Cl(5), [Cu(dbpy)L]Cl(6), (where L = doubly deprotonated hydrazone; phen = 1,10'-phenanthroline; bpy = 2,2'-bipyridine; dbpy = 5,5'-dimethyl-2,2'-bipyridine) have been synthesized. The compounds were characterized by elemental analysis, spectroscopic methods and in the case of crystalline products by X-ray crystallography. The cytotoxicity and topoisomerase I (topo I) inhibition activities of these compounds were studied. It is noteworthy that the addition of N,N-ligands to the copper(II) complex lead to the enhancement in the cytotoxicity of the compounds, especially against human prostate adenocarcinoma cell line (PC-3). Complex 4 exhibits the highest activity against PC-3 with the IC50 value of 3.2 µΜ. The complexes can also inhibit topo I through the binding to DNA and the enzyme.
Subject(s)
Copper/chemistry , Hydrazones/chemistry , Hydrazones/pharmacology , Phosphorus/chemistry , Topoisomerase I Inhibitors/chemistry , Topoisomerase I Inhibitors/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Ligands , Magnetic Resonance Spectroscopy , Models, Molecular , Spectrophotometry, InfraredABSTRACT
Naturally occurring anthraquinones, damnacanthal (1) and nordamnacanthal (2) were synthesized with modified reaction steps and investigated for their cytotoxicity against the MCF-7 and K-562 cancer cell lines, respectively. Intermediate analogues 2-bromomethyl-1,3-dimethoxyanthraquinone (5, IC50 = 5.70 ± 0.21 and 8.50 ± 1.18 mg/mL), 2-hydroxymethyl-1,3-dimethoxyanthraquinone (6, IC50 = 12.10 ± 0.14 and 14.00 ± 2.13), 2-formyl-1,3-dimethoxyantharquinone (7, IC50 = 13.10 ± 1.02 and 14.80 ± 0.74), 1,3-dimethoxy-2-methylanthraquinone (4, IC50 = 9.40 ± 3.51 and 28.40 ± 2.33), and 1,3-dihydroxy-2-methylanthraquinone (3, IC50 = 25.60 ± 0.42 and 28.40 ± 0.79) also exhibited moderate cytotoxicity against MCF-7 and K-562 cancer cell lines, respectively. Other structurally related compounds like 1,3-dihydroxyanthraquinone (13a, IC50 = 19.70 ± 0.35 and 14.50 ± 1.28), 1,3-dimethoxyanthraquinone (13b, IC50 = 6.50 ± 0.66 and 5.90 ± 0.95) were also showed good cytotoxicity. The target compound damnacanthal (1) was found to be the most cytotoxic against the MCF-7 and K-562 cancer cell lines, with IC50 values of 3.80 ± 0.57 and 5.50 ± 1.26, respectively. The structures of all compounds were elucidated with the help of detailed spectroscopic techniques.
Subject(s)
Aldehydes/chemistry , Anthraquinones/chemistry , Aldehydes/pharmacology , Anthraquinones/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Inhibitory Concentration 50 , Molecular StructureABSTRACT
The complete molecule of the title compound, C(18)H(20)N(2)O(4), is generated by inversion symmetry. The conformation around the C=N bond is E. With the exception of the eth-oxy substituent, the mol-ecule is essentially planar with an r.m.s. deviation of 0.0455â Å. In the crystal, mol-ecules are linked by O-Hâ¯N hydrogen bonds into a two-dimensional supra-molecular network parallel to the bc plane.
ABSTRACT
The mol-ecule of the title compound, C(20)H(16)N(2)O(2), is centrosymmetric, the inversion center being located at the mid-point of the central azine bond. The conformation around the C=N bond is E. The whole mol-ecule (except for the H atoms) is essentially planar, with an r.m.s. deviation of 0.07â Å. In the crystal, mol-ecules are linked head-to-tail by pairs of C-Hâ¯O hydrogen bonds, forming inversion dimers, and resulting in the formation of chains propagating along [011].
ABSTRACT
In the zwitterionic title compound, C(18)H(16)N(2)O(4), the dihedral angle between the planes of the benzene and indole rings is 26.38â (10)°. An intra-molecular N-Hâ¯O hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked through N-Hâ¯O, O-Hâ¯O and C-Hâ¯O hydrogen bonds into infinite chains propagating in [010].
ABSTRACT
In the title compound, C(22)H(19)N(3)O(2), the phenol ring forms dihedral angles of 88.93â (10) and 87.95â (12)° with the benzimidazole system and the quinazoline benzene ring, respectively. In the crystal, mol-ecules are linked via O-Hâ¯N hydrogen bonds into infinite chains along [100]. An intra-molecular N-Hâ¯O hydrogen bond generates an S(6) ring.
ABSTRACT
In the zwitterionic title compound, C(18)H(16)N(2)O(4)·H(2)O, the dihedral angle between the planes of the benzene and indole rings is 39.20â (8)°. An intra-molecular N-Hâ¯O hydrogen bond generates an S(6) ring motif. In the crystal, inter-molecular hy-droxy and water O-Hâ¯O(carboxyl-ate) and N(+)-Hâ¯O(carboxyl-ate) and indole N-Hâ¯O(water) hydrogen bonds give a three-dimensional structure.
ABSTRACT
NMR measurements ((119)Sn chemical shift, line width and (13)C relaxation) were made on triphenyltin chloride in two solutions, 2.5 and 0.75 mol% in CDCl(3), at several temperatures. The (13)C spin-lattice relaxation time and NOE data for the phenyl carbons provide the corresponding correlation times for the overall molecular reorientational motion and the internal rotation of the phenyl groups. The results are indicative of a weak intermolecular association of the triphenyltin chloride molecules in solution and are discussed with reference to a model for intermolecular phenyl ring π-π stacking interactions.
Subject(s)
Organotin Compounds/analysis , Isotopes , Magnetic Resonance Spectroscopy , Solutions , TinABSTRACT
The coordination geometry at the Mo(VI) atom in the title compound, [Mo(C(16)H(14)N(2)O(4))O(2)(C(2)H(6)OS)], is distorted octa-hedral. The phenolate O, imino N, oxide O from the enolized carbonyl group and one of the terminal O atoms form the equatorial plane; the axial positions are occupied by the other terminal O atom of the dioxidomolybdenum group and the donor O atom of DMSO. The O=Mo=O angle is 105.31â (6)°. An intra-molecular O-Hâ¯N hydrogen bond and weak inter-molecular C-Hâ¯O hydrogen bonds are present in the structure.
ABSTRACT
In the title salt, [C(6)H(5)N(CH(3))(3)][Sn(2)Br(5)(C(7)H(6)Br)(4)], the Sn(IV) atoms of the dinuclear anion are bridged by a Br atom; the Sn-Br(bridge) bond lengths are 2.9818â (5) and 3.0470â (5)â Å. Both Sn atoms show a distorted cis-trigonal-bipyramidal coordination geometry that is distorted towards a square pyramid. In the crystal, weak C-Hâ¯π inter-actions occur between anions and cations.
ABSTRACT
The dinuclear compound, [V(2)(C(12)H(11)BrN(2)O(2))(2)(CH(3)O)(2)O(2)], lies on a center of inversion. The doubly-deprotonated Schiff base O,N,O'-chelates to the V(V) atom; two metal atoms are bridged by the methoxide units. The coordination geometry is a distorted octa-hedron. Weak inter-molecular C-Hâ¯N hydrogen bonding is present in the crystal structure. The bromo-phenyl unit is disordered over two positions, with the major component being in a 0.909â (6) proportion.