Synthesis of hybrid fluoroquinolone-boron complexes and their evaluation in cervical cancer cell lines

Quinolones are a family of antimicrobial agents that have been used in antibacterial and anticancer chemotherapy. Fluoroquinolone targets DNA gyrase and topoisomerase IV enzymes affecting several cellular processes, like cell death and proliferation; the best way to act is in the form of carboxylic acid or, recently, as quinolone-metal complex. In this work, the use of boron is shown as an alternative of metal to form a complex by incorporating to fluoroquinolone as an electron withdrawing substituent to activate the C-7 position chemoselectively for the production of new fluoroquinolone hybrids and test their effects on cell proliferation. Fluoroquinolone-boron complexes were synthesized according to the Gould-Jacobs cyclization method, and five hybrid fluoroquinolone-boron compounds were obtained by S N Ar reaction, yielding 31 to 46%25, at 80°C, and in 10 to 25 hours of reaction. The effect of the five fluoroquinolone-boron hybrids was evaluated in cervical cancer cell lines by cell proliferation assay. 7-hydantoin-fluoroquinolone-boron and 7-dihydropyridine-fluoroquinolone-boron complexes showed the strongest effect according to dose-response assay, respectively. The fluoroquinolone-boron hybrid complex showed proliferation inhibition in SiHa and CasKi cells, opening the possibility to use them as potential agents for the treatment of cancer. © 2019 Hiram Hernández-López et al.

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