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The one-pot biscycloaddition of alkyl-tethered diglycines to C 60 provided five series of bridged bis(pyrrolidino)fullerenes with good regioselectivity, giving mainly cis -2 and cis -3 products. An influence of the bridge length and addition pattern on spectroscopic properties, as well as on the shape of hierarchically organized supramolecular structures was observed. Additional investigation of all synthesized compounds confirmed their strong in vitro antioxidant activity 4–10-fold better than the standard antioxidant vitamin C. [ABSTRACT FROM AUTHOR]

The present study reports the synthesis, spectral characterization, self-assembly properties, and preliminary in vitro study of antioxidant capacity of two triple covalent hybrids consisting of fullerene C 60 , peptide, and steroidal moiety. Previously synthesized fulleropyrrolidinic acid and pregnenolone were connected by peptide linker using a multistep DCC/DMAP and/or EDC/HOBT esterification/amidation procedure. The hybrids were characterized by comparative analysis of spectroscopic data obtained from FTIR, UV–vis, HRMS, and extensive NMR experiments ( 1 H, 13 C, COSY, HSQC, and HMBC). The self-assembling properties and morphology of triads samples prepared by drop-drying method were examined by scanning electron microscopy (SEM). Preliminary in vitro antioxidant activity was studied by Ferrous ion Oxidation-Xylenol orange (FOX) method. [ABSTRACT FROM AUTHOR]

Abstract: The present study is concerned with the oxidative behaviour of unsaturated and epoxy 5-oxo-5,10-secosteroids in the presence of m-CPBA or TFAA-UHP as oxidants in order to investigate potential parameters controlling the chemoselectivity and regioselectivity. In the study we discovered a striking difference in the chemical behaviour of stereoisomeric compounds, (Z)- and (E)-3β-acetoxy-5,10-secocholest-1(10)-en-5-ones, as well as 1S,10R- and 1R,10R-epoxides. The secoketones were oxidized with exclusively C-6 migration and Baeyer–Villiger rearrangement product formation, whereas their stereoisomers provided the ring-contracted products, without lactone formation. The preferred conformation of expanded and contracted rings was established by NOESY correlations. The structures of two obtained lactones were also confirmed by X-ray analysis. The mechanistic and stereochemical aspects of these transformations are discussed. [Copyright &y& Elsevier]

Abstract: The reactions of 17α-hydroxyprogesterone with Lawesson’s reagent (LR) in toluene, CH2Cl2 and/or CCl4 gave, depending on the duration of the reaction, two diastereoisomeric androst-4-en-17-spiro-1,3,2-oxathiaphospholane-2-sulfide pairs 2a,b and 3a,b in approximately 7:3 ratio, differing in configuration at the phosphorus atom. A parallel analysis of heteronuclear 2D 1H–13C spectra (HSQC and HMBC) and homonuclear 2D spectra (NOESY) enabled complete 1H and 13C assignments of each isomer. Also, analysis of NOESY correlations provided evidence for the preferred conformation. X-ray analysis of 3a confirmed the structure and absolute configuration on phosphorus. A pathway for the formation of 1,3,2-oxathiaphospholane ring was proposed. Cytotoxic activity in vitro was tested against three tumor cell lines (human cervix carcinoma HeLa cells and two human breast carcinoma MDA-MB-361 and MDA-MB-453 cells). Compound 3a and mixture 3a,b showed a moderate activity against HeLa and MDA-MB-453 cell lines while against MDA-MB-361 cell line all tested compounds exerted very weak cytotoxic effect. Antimicrobial activity against Gram-positive, Gram-negative bacteria and fungal cells, toxicity to brine shrimp Artemia salina, were evaluated. All tested compounds showed strong antifungal activity. [Copyright &y& Elsevier]

Abstract: In this paper a synthetic pathway to the modified 5,10:13,14-bisfragmentation cholestane derivatives 8–14 is described. The synthesis involves introduction of the 5α- and 14α-hydroxyl groups in the cholestane molecule and subsequent cleavage of the C(5)–C(10) bond in 5α,14α-dihydroxycholestan-3β-yl acetate (4) with the HgO/I2 reagent and the C(13)–C(14) bond in the stereoisomeric 14α-hydroxy-5,10-secosteroids 5 and 6 with the Pb(OAc)4/I2 reagent. Complete and unambiguous 1H and 13C NMR resonance assignments of the obtained secosteroids, as well as the solution conformations of their 10- and 9-membered rings were determined by extensive analysis of 1D and 2D NMR spectral data. The structures and the solid-state conformations of 5,10-secosteroids 5–7 were confirmed by X-ray analysis. All diseco-compounds have a novel 5,10:13,14-disecocholestane skeleton. [Copyright &y& Elsevier]

Abstract: We report herein the synthesis of a novel modified steroid with two rigidly positioned amino acids in C- and N-protected forms (Gly–O t Bu and N-Fmoc–l-Phe) at the angular positions (C-18 methylamino group and C-19 carboxylic function) of the steroid nucleus via amide bonds, starting from 18-cyanopregnenolone acetate over 10 steps. In an attempt to gain more insight into the structural and conformational features of this novel 18-Phe,19-Gly-containing steroidal compound, we describe the detailed 2D NMR spectral analysis. Despite the large size and the conformational flexibility of the amino acid units in this molecule, conformational analysis by NOESY connectivities showed the existence of mainly one conformation (∼95%) in CDCl3 solution with approximately parallel orientation of the phenylalanine and glycine moieties. [Copyright &y& Elsevier]

Abstract: Four new fullero-steroids were synthesized starting from γ-aminobutyric acid (GABA)-incorporated fulleropyrrolidine and corresponding sterols. The synthesis, characterization, preliminary study on in vitro antioxidant activity as well as the steady state photophysical properties are presented. All synthesized compounds showed antioxidant activity 2–3-fold higher than the parent fullerene. The most active compound appeared to be as potent as standard antioxidant BHT (2,6-di-tert-butyl-4-methylphenol). Also, all of them fluoresce 6–8-fold stronger than C60, thus representing potential irradiation assisted pro-oxidants. With significantly increased lipophilicity, it could be expected that attached steroidal subunit enables better penetration of C60 to living cell membranes, thus facilitating its antioxidant activity. Based on all obtained results, newly synthesized covalent fullero-steroidal conjugates represent good candidates for potential antioxidants as well as pro-oxidants. [Copyright &y& Elsevier]

Abstract: The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3) and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B-homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for their possible effects against two human tumor cell lines, cervical carcinoma (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1–6, exerted a dose-dependent antiproliferative effect toward cell lines used in experimental design, showing high selectivity in their action for tumor cells in comparison to normal immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2, 3 and 4 exhibited a very high but selective antitumor activity, by inducing apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells). Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control, healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible reasons for profound differences in the effects of this spectrum of steroidal compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs are discussed. The molecular mechanisms for apoptotic events in HeLa cell line are suggested. The guidelines for further research are underlined. [Copyright &y& Elsevier]

Four macrocyclic bis(pyrrolidino)fullerene regioisomers with e -edge, e -face, trans -4 and cis -2 addition patterns were synthesized from the corresponding monoadduct by Prato's cycloaddition in a yield of 50%, and fully characterized by spectroscopic techniques. Bisadduct regioisomers were isolated easily in a pure form using dry-flash column chromatography. The relative ratio of the isolated regioisomers e -edge/ e -face/ trans -4/ cis -2 was 1.0:1.9:1.5:4.9. Morphology of self-assembled structures of the four bisadduct regioisomers in solution was characterized using scanning electron microscopy. [ABSTRACT FROM AUTHOR]

• Polysaccharides (PS) levan and pullulan were hydrophobized by cholesterol. • New C 60 -PS non-covalent hybrid NPs were synthesized and studied by DLS and SEM. • The size of C 60 -PS NPs in water was reduced compared to starting PS NPs. • DPPH radical scavenging and β-carotene bleaching abilities of NPs were studied. • The antioxidant potency increases with the growing hydrophobicity. An efficient encapsulation of the fullerene into two hydrophobized and one native polysaccharide provided water soluble supramolecular hybrids. After covalent modification of polysaccharides by cholesterol, noncovalent hybrids were prepared by a three-step procedure, including mixing of individual aqueous solutions of hydrophobized, as well as native sugar with solution of the fullerene in pyridine, dialysis and lyophilization. Although the degree of the fullerene incorporation into hydrophobized substrates, cholesterol-levan and cholesterol-pullulan, was lower in comparison to the native polysaccharide levan, hydrophobization provided nanoparticles with improved properties. The particle size distribution, studied by dynamic light scattering and scanning electron microscopy revealed formation of moderately polydisperse aggregates, with the diameter contraction in comparison to the corresponding free polysaccharide, especially in the case of hydrophobized substrates. The morphological examination, done by scanning electron microscopy indicated the self-organization of the fullerene-native polysaccharide to round individual structures, while fullerene-hydrophobized polysaccharide hybrids tend to form networks. The antioxidant activity of the synthesized polysaccharide-C 60 noncovalent hybrids versus starting polysaccharides was investigated by the DPPH radical scavenging and the β-carotene-linoleic acid bleaching methods. In all three complexes, the radical scavenging ability of the fullerene remained preserved, and a positive effect of levan hydrophobization was observed. [ABSTRACT FROM AUTHOR]