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Two series of polydentate N,O,S-ligands containing thiourea fragments attached to a p-cresol scaffold, unsymmetrical mono-acylated bis-amines and symmetrical bis-thioureas, are obtained by common experiments. It is observed that the reaction output is strongly dependent on both bis-amine and thiocarbamic chloride substituents. The products are characterized by 1D and 2D NMR spectra in solution and by single crystal XRD. A preliminary study on the coordination abilities of selected products is performed by ITC at around neutral media. [ABSTRACT FROM AUTHOR]

A study on the functionalisation of 2-mercapto-5-methyl-1,3,4-thiadiazole has been conducted, yielding two series of products: 2-(ω-haloalkylthio)thiadiazoles and symmetrical bis-thiadiazoles, with variable chain lengths. The experimental conditions were optimised for each class of compounds by altering the base used and the reagents' proportions, leading to the development of separate protocols tailored to their specific reactivity and purification needs. The target halogenide reagents and bis-thiadiazole ligands were obtained either as single products or as mixtures easily separable by chromatography. Characterisation of the products was performed using 1D and 2D NMR spectra in solution, complemented by single crystal X-ray diffraction (XRD) for selected samples, to elucidate their structural properties. [ABSTRACT FROM AUTHOR]

The title compound 1-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-2-oxoethyl) quinolin-1-ium bromide was obtained in good yield by a facile one-pot, one-step synthetic procedure involving quinoline and an aromatic α-bromo ketone. The product was isolated using hot recrystallization from acetone/acetonitrile solution and characterized using powder and single-crystal XRD, 1D and 2D NMR, DSC, FT-IR, and HRMS analyses. [ABSTRACT FROM AUTHOR]

In this study, three series of polydentate N,O-ligands possessing unsymmetrical urea fragments attached to a p-cresol scaffold are obtained, namely mono- and bi-substituted open-chain aromatics, synthesised using a common experiment, as well as fused aryloxazinones. Separate protocols for the preparation of each series are developed. It is found that in the case of open-chain compounds, the reaction output is strongly dependent on both bis-amine and carbamoyl chloride substituents, while oxazinones can be effectively obtained via a common protocol. The products are characterized via 1D and 2D NMR spectra in solution and using single-crystal XRD. A preliminary study on the coordination abilities of the products performed via ITC shows that there are no substantial interactions in the pH range of 5.0–8.5 in general. [ABSTRACT FROM AUTHOR]

The novel compound 3-methyl-1-phenyl-4-thioacetylpyrazol-5-one is obtained in excellent yield via a thionation of the corresponding oxygen analogue. The product is isolated in pure form using column chromatography and is characterised using 1D and 2D NMR experiments, ATR IR and HRMS spectra, and single-crystal XRD. [ABSTRACT FROM AUTHOR]

The novel compound 2-(1H-imidazol-2-yl)-2,3-dihydro-1H-perimidine was obtained in very good yield via a known eco-friendly protocol. The product was isolated in pure form as a solvate by simple filtration from the crude mixture. Its structure was assigned by 1D and 2D NMR experiments and was confirmed by high resolution MS and single crystal XRD. The temperature of methanol release was determined by DSC and the energy of the process theoretically estimated. [ABSTRACT FROM AUTHOR]

The novel compound 4-methyl-7-((2-((5-methyl-1,3,4-thiadiazol-2-yl)thio)ethyl)thio)-coumarin is obtained in good yield via a two-step protocol; that is, initial synthesis of the reagent 2-((2-chloroethyl)thio)-5-methyl-1,3,4-thiadiazole followed by alkylation of 7-mercapto-4-methylcoumarin. The product's structure is assigned by 1D and 2D NMR experiments and is confirmed by single-crystal XRD. [ABSTRACT FROM AUTHOR]

A series of acylpyrazolones possessing a methylene bridged heterocyclic unit in the acyl fragment are synthesized and characterized in solution and the solid state. It is found that the products exist in the solid state as intramolecular or intermolecular zwitterions between the tautomeric pyrazolone hydroxyl group and the nitrogen atom of the acyl substituents. Aliphatic amine units with a variable number and type of heteroatoms and ring size are attached and the type of zwitterions formed are analysed by single crystal XRD. It is observed that the products coordinate spontaneously with cesium carbonate being used as a base. These complexes are also studied by XRD. [ABSTRACT FROM AUTHOR]

Here, we describe the synthesis, characterization, and biological activities of a series of 26 new styryl-2(3H)-benzothiazolone analogs of combretastatin-A4 (CA-4). The cytotoxic activities of these compounds were tested in several cell lines (EA.hy926, A549, BEAS-2B, MDA-MB-231, HT-29, MCF-7, and MCF-10A), and the relations between structure and cytotoxicity are discussed. From the series, compound (Z)-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3H)-benzothiazolone (26Z) exhibits the most potent cytotoxic activity (IC50 0.13 ± 0.01 µM) against EA.hy926 cells. 26Z not only inhibits vasculogenesis but also disrupts pre-existing vasculature. 26Z is a microtubule-modulating agent and inhibits a spectrum of angiogenic events in EA.hy926 cells by interfering with endothelial cell invasion, migration, and proliferation. 26Z also shows anti-proliferative activity in CA-4 resistant cells with the following IC50 values: HT-29 (0.008 ± 0.001 µM), MDA-MB-231 (1.35 ± 0.42 µM), and MCF-7 (2.42 ± 0.48 µM). Cell-cycle phase-specific experiments show that 26Z treatment results in G2/M arrest and mitotic spindle multipolarity, suggesting that drug-induced centrosome amplification could promote cell death. Some 26Z-treated adherent cells undergo aberrant cytokinesis, resulting in aneuploidy that perhaps contributes to drug-induced cell death. These data indicate that spindle multipolarity induction by 26Z has an exciting chemotherapeutic potential that merits further investigation. [ABSTRACT FROM AUTHOR]

Three new molecular complexes (phen)3(2-amino-Bz)2(H+)(BF4−)·3H2O 5, (phen)3(2-amino-5(6)-methyl-Bz)2(H+)(BF4−)·H2O 6, and (phen)(1-methyl-2-amino-Bz)(H+)(BF4−) 7, were prepared by self-assembly of 1,10-phenanthroline (phen) and various substituted 2-aminobenzimidazoles. Confirmation of their structures was established through spectroscopic methods and elemental analysis. The X-ray diffraction analysis revealed that the crystal structure of 7 is stabilized by the formation of hydrogen bonds and short contacts. In addition, the molecular geometry and electron structure of molecules 5 and 6 were theoretically evaluated using density functional theory (DFT) methods. According to the DFT B3LYP/6-311+G* calculations, the protonated benzimidazole (Bz) units act as NH hydrogen bond donors, binding two phenanthrolines and a BF4− ion. Non-protonated Bz unit form hydrogen bonds with the N-atoms of a third molecule phen. The molecular assembly is held together by π-π stacking between benzimidazole and phenanthroline rings, allowing for N-atoms to associate with water molecules. The complexes were tested in vitro for their tumor cell growth inhibitory effects on prostate (PC3), breast (MDA-MB-231 and MCF-7), and cervical (HeLa) cancer cell lines using MTT-dye reduction assay. The in vitro cytotoxicity analysis and spectrophotometric investigation in the presence of ct-DNA, showed that self-assembled molecules 5–7 are promising DNA-binding anticancer agents warranting further in-depth exploration. [ABSTRACT FROM AUTHOR]

Herein, the synthesis and characterization of four novel 5,5′-diphenylhydantoin Schiff bases containing different aromatic species are presented. Their structure–property relationship was studied by X-ray, optical and electrochemical methods as well as DFT calculations in terms of their E/Z photoisomerization and enol/keto phototaumerization. The big challenge in photoinduced motion is achieving control and stability over the two isomers. Solvent-driven bidirectional photoswitching behavior was studied in nonpolar 1,4-dioxane and polar aprotic DMF. T-type photochromism in 1,4-DOX and opposite behavior in DMF as P-type switches (bistable system) were observed. The obtained results lead to a conclusion that by variation of the solvent environment a direct control over the bidirectional switching behaviour from T-type to P-type can be achieved. [ABSTRACT FROM AUTHOR]

The present study reports the synthesis and structural, photophysical and electrochemical properties of five new Schiff bases containing hydantoin rings. The compounds were synthesized via condensation reactions between 3-amino-5,5′-dimethylhydantoin and five different aromatic aldehydes. All compounds were characterized using different spectroscopic and electrochemical tools as well as single crystal X-ray diffraction analysis. The photochromic and molecular switching behaviours of the switchable –CH=N– groups of Schiff bases were investigated by real time UV-vis spectroscopy in DMF under long wavelength UV light at λ = 365 nm for 90 min (mostly E → Z) and dark relaxation at room temperature for 60 min (mostly Z → E) in the spectral region of 250 nm to 600 nm at equal concentrations. The electrochemical properties of the compounds were investigated on a glassy platinum electrode (Pt-) in DMF using the cyclic voltammetric (CV) technique before and after UV irradiation. The effects of functional groups on the reduction potential of the Schiff bases are discussed. Electrochemical studies showed that the reduction of –CH=N groups is mostly quasi-reversible, with adsorption-controlled processes for (E)-3-((2-hydroxybenzylidene)amino)-5,5′-dimethylimidazolidine-2,4-dione (SB2) and (E)-3-((4-(dimethylamino)benzylidene)amino)-5,5′-dimethylimidazolidine-2,4-dione (SB4) and intermediate processes for the remaining compounds. [ABSTRACT FROM AUTHOR]

In order to design and synthesize a new class of heterocyclic analogues of natural combretastatin A-4 and its synthetic derivative AVE8062, the benzoxazolone ring was selected as a scaffold for a bioisosteric replacement of the ring B of both molecules. A library of 28 cis - and trans -styrylbenzoxazolones was obtained by a modified Wittig reaction under Boden's conditions. Structures of the newly synthesized compounds bearing the 3,4,5-trimethoxy-, 3,4-dimethoxy-, 3,5-dimethoxy-, and 4-methoxystyryl fragment at position 4, 5, 6 or 7 of benzoxazolone core were determined on the basis of spectral and X ray data. The in vitro cytotoxicity of styrylbenzoxazolones against different cell lines was examined. Stilbene derivative 16 Z , ( Z )-3-methyl-6-(3,4,5-trimethoxystyryl)-2(3 H )-benzoxazolone, showed highest antiproliferative potential of the series, with IC 50 of 0.25 μM against combretastatin resistant cell line HT-29, 0.19 μM against HepG2, 0.28 μM against EA.hy926 and 0.73 μM against K562 cells. Furthermore, the results of flow cytometric analysis confirmed that 16 Z induced cell cycle arrest in G2/M phase in the cell lines like combretastatin A-4. This arrest is followed by an abnormal exit of cells from mitosis without cytokinesis into a pseudo G1-like multinucleate state leading to late apoptosis and cell death. Accordingly, synthetic analogue 16 Z was identified as the most promising potential anticancer agent in present study, and was selected as lead compound for further detailed investigations. [ABSTRACT FROM AUTHOR]