The Cytotoxic Properties of Some Tricyclic 1,3-Dithiolium Flavonoids.

BACKGROUND: Due to the emergence of multidrug resistant microorganisms, new classes of antibiotics are needed. In this paper, we present the cytotoxic effects of five tricyclic flavonoids, one of which was previously identified as a potent antimicrobial agent. METHODS: All five derivatives were tested against human HOS and MCF7 cancer cell lines using a wound scratch assay. The cytotoxic properties of previously reported flavonoid 4a were also evaluated using the standard MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) and live/dead assays, using NHDF, HOS and MCF7 cell lines. RESULTS: All five derivatives were found to inhibit to some degree the proliferation of cancer cells. 4a was also found to be less toxic towards regular versus cancerous human cells. Moreover, the minimum bactericidal concentration of 4a against Staphylococcus aureus was found to be non-toxic for any of the tested human cell lines. CONCLUSIONS: Derivative 4a has the potential of being used as a therapeutic agent against certain microorganisms. Further structure optimization is required for use against tumors.

Tetrathiafulvalene-[2.2]paracyclophanes: Synthesis, crystal structures, and chiroptical properties.

Two racemic tetrathiafulvalene-[2.2]paracyclophane electron donors EDT-TTF-[2.2]paracyclophane 1 and (COOMe)2 -TTF-[2.2]paracyclophane 2 have been synthesized via the phosphite mediated cross coupling strategy. Chiral HPLC allowed the optical resolution of the (RP ) and (SP ) enantiomers for both compounds. Solid-state structures of (RP )-1 and (rac)-2 have been determined by single crystal X-ray analysis. Intermolecular π-π and S•••S interactions are disclosed in the packing. Single crystal X-ray analysis of (RP )-1 combined with experimental and theoretical circular dichroism spectra allowed the assignment of the absolute configuration of the enantiomers of 1 and 2.

[2.2]Paracyclophane-Bis(triazole) Systems: Synthesis and Photochemical Behavior.

Mono-, pseudo-gem, and pseudo-para ethynylcyclophanes and bis(azides) have been employed as addition partners in CuAAC reactions to design and build complex extended molecular scaffolds. The reactivity of the resulting triazoles was investigated under photochemical conditions. A variety of newly substituted [2.2]paracyclophanes were identified; deazotization of pseudo-gem and pseudo-para adducts provided indolophane derivatives. An intramolecular stabilization effect was observed in the case of pseudo-gem derivatives. A photochemical rearrangement from a pseudo-para adduct to a pseudo-ortho product was identified.

Antibacterial structure-activity relationship studies of several tricyclic sulfur-containing flavonoids.

A structure-activity relationship study concerning the antibacterial properties of several halogen-substituted tricyclic sulfur-containing flavonoids has been performed. The compounds have been synthesized by cyclocondensation of the corresponding 3-dithiocarbamic flavanones under acidic conditions. The influence of different halogen substituents on the antibacterial properties has been tested against Staphylococcus aureus and Escherichia coli. Amongst the N,N-dialkylamino-substituted flavonoids, those having an N,N-diethylamino moiety exhibited good to excellent antimicrobial properties against both pathogens. Fluorine-substituted flavonoids were found to be less active than those bearing other halogen atoms.

[2.2]Paracyclophane derivatives containing tetrathiafulvalene moieties.

The synthesis of [2.2]paracyclophane derivatives containing tetrathiafulvalene units has been accomplished by the coupling reaction of 4-([2.2]paracyclophan-4-yl)-1,3-dithiol-2-thione in the presence of trimethylphosphite. The 1,3-dithiol-2-thione derivative was in turn synthesized by the regioselective bromination of 4-acetyl[2.2]paracyclophane, then through the corresponding dithiocarbamates and 1,3-dithiolium salts.

Selenium halide-induced bridge formation in [2.2]paracyclophanes.

An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo-exo-diene substructure. The reactions have been found to be sensitive to the substitution of the ethynyl group. The formation of dienes with a zig-zag configuration is related to that observed for non-conjugated cyclic diynes of medium ring size.

A facile synthesis of Pechmann dyes.

A facile synthesis of Pechmann dyes has been accomplished by the reaction of substituted N-phenacyl-4-dimethylaminopyridinium halides with dimethyl maleate in the presence of DBU. Based on a related 4-DMAP elimination product and an isolated monolactone intermediate a reaction mechanism has been proposed. The scope of this synthetic method is determined by the availability of α-haloaroyl or heteroaroyl derivatives. DBU=1,8-diazabicycloundec-7-ene, DMAP=4-dimethylaminopyridine.

The antibacterial properties of sulfur containing flavonoids.

Some dithiocarbamic esters bearing a flavanone backbone, as well as their corresponding 1,3-dithiolium salts were tested against Staphylococcus aureus and Escherichia coli. The 1,3-dithiolium tricyclic flavonoids display good inhibitory properties against both Gram-positive and Gram-negative pathogens.

5-Bromo-4-(3,5-di-bromo-2-hy-droxy-phen-yl)-2-(piperidin-1-yl)-1,3-di-thiol-2-ylium bromide.

In the title salt, C14H13Br3NOS2 (+)·Br(-), synthesized by bromination of mesoionic 2-[2-(piperidin-1-yl)-1,3-di-thiol-2-ylium-4-yl]phenolate in glacial acetic acid, the dihedral angle between the 1,3-di-thiol-ium ring and the phenolic substituent ring is 45.9 (3)° due to the steric influence of the ortho-Br group on the 1,3-di-thiol-ium ring. The piperidine ring adopts a chair conformation. In the crystal, the cation and anion are linked by an O-H⋯Br hydrogen bond.

rac-1-(5-Bromo-2-hy-droxy-phen-yl)-1-oxopropan-2-yl morpholine-4-carbo-dithio-ate.

In the racemic title compound, C14H16BrNO3S2, synthesized from the corresponding ω-bromo-propio-phenone, the dihedral angle between the plane of the phenol group and that of the planar section [maximum deviation = 0.040 (2) Å] of the morpholine-4-carbodi-thiol-ate moiety is 76.36 (10)°. A strong intra-molecular phenol O-H⋯O hydrogen bond if present in the mol-ecule. In the crystal, only weak C-H⋯S and C-H⋯O inter-actions are found.

4-Bromo-2-[5-methyl-2-(morpholin-4-yl)-1,3-thia-zol-4-yl]phenol.

In the title compound, C14H15BrN2O2S, synthesized by the reaction of the corresponding phenacyl thio-cyanate with morpholine, the dihedral angle between the 1,3-thia-zole ring and the phenolic substituent ring is 23.46 (10)° as a result of the steric influence of the ortho-methyl group on the thia-zole ring. A strong intra-molecular phenolic O-H⋯N hydrogen bond is present in the mol-ecule. In the crystal, a weak C-H⋯Ophenol hydrogen bond gives rise to chains lying parallel to [20-1]. A short inter-molecular Br⋯Omorpholine inter-action is also present [3.1338 (19) Å].