Benzoxaboroles as dynamic covalent receptors for bioconjugation and transport of nucleosides and related drugs: proof of action in HeLa cells

CECILIA SAMANIEGO LOPEZ; MARTÍNEZ, JIMENA HEBE; SOFIA LORENA ACEBEDO; CARLA C. SPAGNUOLO

BIOORGANIC CHEMISTRY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2019 vol. 90 p. 103059 - 103064

0045-2068

In this work we describe not previously explored binding studies on the reversible interaction of benzoxaborole and functional derivatives including a near infrared fluorescent boro-nolectine, Cy-Bx, with ligands of medical and pharmaceutical interest such as nucleosidic drugs gemcitabine and capecitabine, as well as the hydrophobic chemotherapeutic doxorubicin. The dynamic covalent interaction in physiological conditions was assessed by spectroscopic techniques yielding moderate to high binding affinities. The cytotoxic activity of the drugs upon conju-gation to the boronolectins was evaluated revealing significant influence of the bioconjugation status on the cellular viability. By dual observation of the intrinsic green fluorescence emission of doxorubicin and the near-infrared emission of Cy-Bx, the availa-bility of conjugate for cellular uptake and localization in the mod-el cancer cell line HeLa was assesed by fluorescence imaging. Benzoxaborole and the fluorescent boronolectin Cy-Bx, proved to be versatile conjugation tools for 1,2 and 1,3-diol containing pharmacophores as well as bioisosteric forms such as 1,2-hydroxyamino, envisioning these small boronolectins as compo-nents in systems for drug release with tracking capability