Tatjana Kop

Synthesis and antiproliferative activity of epoxy and bromo compounds derived from estrone.

Based on biological properties of epoxyquinols from natural sources, bromo and epoxyquinols derived from estrone were synthesized and screened against Fem-X, HeLa and K(562) cell lines. Evidence was found that the bromine atom and the epoxy moiety significantly increase the antiproliferative activity within the series.

Estrone derived steroidal diepoxide: biologically active compound and precursor of a stable steroidal A,B-spiro system.

A simple approach to a stable steroidal estrone derived A,B-spiro system is reported. Treatment of estrone derived A-ring diepoxyalcohol with the Ac(2)O-TMSOTf system at the ambient temperature led to acetylation, while at the reflux temperature the acid-catalysed rearrangement took place affording the spiro-compound. Results of extensive in vitro and in vivo anticancer tests on the diepoxide, as well as preliminary data on the antiproliferative activity of the spiro-product against three cancer cell lines, are also presented.

Electrochemical, theoretical, and morphological studies of antioxidant fullerosteroids

Four fullerosteroidal conjugates, previously confirmed to express two- to threefold better antioxidant activity in vitro than C60, were subjected to additional studies, including electrochemical, theoretical, and morphological examination. All tested compounds underwent reversible, diffusion-controlled reductions. A notable influence of the solvent properties on the reduction potential, the level of aggregation, and the lowest unoccupied molecular orbital (LUMO) energy was observed. Theoretical calculations indicated that the energy gain obtained by an intermediate formation, together with compounds’ polarizability, polarity, and lipophilicity contributed to the radical quenching capacity. Very large supramolecular aggregates of all fullerosteroidal esters with no hierarchical arrangement were observed in precipitated samples, while solvent induced self-assembling led to round nanoplates, which further arranged to flower-shaped hierarchically ordered architectures or uniformly distributed discoid particles. As in electrochemical studies, fine tuning of the aggregation level was achieved by the solvent.Graphical abstract

Fulleropyrrolidines derived from dioxa- and trioxaalkyl-tethered diglycines

Two different α,ω-diglicynes linked by linear polyoxaalkyl chains in the presence of formaldehyde underwent Prato reaction to the fullerene C60. The shorter linker templated formation of only cis-bisadducts, while the longer one afforded a mixture of four bisadducts (all cis and the equatorial) and difullerene dumbbell compound. Their structures were confirmed by the extensive analysis of the spectral data and molecular symmetry, as well. All compounds expressed an ability to arrange into hierarchically ordered supramolecular aggregates, the form of which depended both on the addition pattern and the spacer structure. The attenuated electron-accepting affinity, examined by cyclic voltammetry was in agreement with diminished delocalization of the π-electronic system. In addition, all compounds exerted a notable radical scavenging activity.

Fulleropeptide esters as potential self-assembled antioxidants.

Summary The potential use of amphiphilic fullerene derivatives as a bionanomaterial was investigated by cyclic voltammetry (CV), scanning electron microscopy (SEM), and the ferrous ion oxidation–xylenol orange (FOX) method. Despite the disrupted delocalization of the π-electronic system over the C60 sphere, its antioxidant capacity remained high for all twelve derivatives. The compounds expressed up to two-fold and 5–12-fold better peroxide quenching capacity as compared to pristine C60 and standard antioxidant vitamin C, respectively. During precipitation and slow evaporation of the solvent, all compounds underwent spontaneous self-assembly giving ordered structures. The size and morphology of the resulting particles depend primarily on the sample concentration, and somewhat on the side chain structure.

Synthesis and characterization of highly ordered self-assembled bioactive fulleropeptides

A series of N-substituted fulleropyrrolidines containing peptide side chain was synthesized by the quantitative, TFA-mediated deprotection of the corresponding tert-butyl esters. The structures of all compounds were determined by comparative analysis of spectroscopic and spectrometric data. The electrochemical characterization, conducted by cyclic voltammetry at room temperature confirmed slightly attenuated reducibility in comparison to pristine C60 and a weak long-range electron-accepting effect of the Gly3-fragment. The introduction of the peptide subunit led to improved solubility and enabled examination of the antioxidant properties in water environment. A notable radical scavenging activity of the fullerene subunit remained almost unchanged in all compounds. The investigation of the supramolecular self-assembling, performed by the scanning electron microscopy revealed an influence of the side chain, particularly the fraction of the hydrophobic residue, as well as the substrate structure on the final morphology. Most of the compounds underwent highly ordered multi-stage hierarchical assembling to the attractive, flower-shaped supramolecular aggregates during both the precipitation and slow evaporation of the solvent.