Rational Design of Nucleoside-Bile Acid Conjugates Incorporating a Triazole Moiety for Anticancer Evaluation and SAR Exploration.

Herein we report a study on the synthesis and biological evaluation of a library of nucleoside-bile acid conjugates prepared by combining 2'-deoxyadenosine, 2'-deoxyguanosine, 2'-deoxyuridine as well as adenosine and guanosine derivatives with cheno-, urso-, nor-cheno-, nor-urso- and taurourso-desoxycholic acid derivatives by means of the click reaction. The new nucleoside-bile acid conjugates incorporating a triazole moiety were tested in vitro against leukemic K562 and HCT116 colon carcinoma, as well as on normal fibroblast cells. Six compounds displayed interesting anti-proliferative activity against the selected cancer lines and no cytotoxic effects against normal fibroblasts. A possible structure activity relationship was also investigated.

Self-organization, optical, and electrical properties of alpha-quinquethiophene-dinucleotide conjugates.

The synthesis and properties of (5')TA(3')-t5 (8a) and (5')CG(3')-t5 (8b) conjugates, in which the self-complementary dinucleotides TA and CG are covalently bound to the central ring of alpha-quinquethiophene (t5), are described. According to molecular mechanics calculations, the preferred conformation of both 8a and 8b is that with the dinucleotide folded over the planar t5 backbone, with the nucleobases facing t5 at stacking distance. The calculations show that the aggregation process of 8a and 8b is driven by a mix of nucleobase-thiophene interactions, hydrogen bonding between nucleobases (non Watson-Crick (W&C) in TA, and W&C in CG), van der Waals, and electrostatic interactions. While 8b is scarcely soluble in any solvents, 8a is soluble in water, indicating that the aggregates of the former are more stable than those of the latter. Microfluidic-induced self-assembly studies of 8a showed the formation of lamellar, spherulitic, and dendritic supramolecular structures, depending on the concentration and solvent evaporation time. The self-assembled structures displayed micrometer dimensions in the xy plane of the substrate and nanometer dimensions in the z direction. Spatially resolved confocal microscopy and spectroscopy showed that the aggregates were characterized by intense fluorescence emission. Cast films of 8a from water solutions showed chirality transfer from the dinucleotide to t5. The hole mobility of the cast films of 8a was estimated using a two-electrode device under high vacuum and found to be up to two orders of magnitude greater than those previously measured for dinucleotide-quarterthiophene conjugates under the same experimental conditions.

Water-soluble, electroactive, and photoluminescent quaterthiophene-dinucleotide conjugates.

Quaterthiophene-dinucleotide conjugates 5'TA3'-t4-3'AT5', 5'AA3'-t4-3'AA5', and 5'TT3'-t4-3'TT5' (TA: thymidine-adenosine, AA: adenosine-adenosine, TT: thymidine-thymidine) were synthesized and analyzed by a combination of spectroscopy and microscopy, electrical characterization, and theoretical calculations. Circular dichroism (CD) experiments demonstrated a transfer of chirality from the dinucleotides to quaterthiophene at high ionic strength and in cast films. The films were photoluminescent and electroactive. CD and photoluminescence spectra and current density/voltage plots (measured under dynamic vacuum) displayed significant variation on changing the dinucleotide scaffold. Molecular mechanics and molecular dynamics calculations indicated that the conformation and packing modes of the conjugates are the result of a balance between intra- and intermolecular nucleobase-thiophene stacking interactions and intramolecular hydrogen bonding between the nucleobases.