Phosphine derivatives of sparfloxacin – Synthesis, structures and in vitro activity

•We synthesized two sparfloxacin derivatives: phosphine (PSf) and its oxide (OPSf).•Molecular structure of OPSf was determined using X-ray analysis.•DFT calculations were performed for all the compounds.•Antibacterial activity was studied against several reference and clinical strains.•OPSf exhibited a high cytotoxic activity against CT26 and A549 cancer lines.

We synthesized two derivatives of sparfloxacin (HSf): aminomethyl(diphenyl)phosphine (PSf) and its oxide (OPSf). The compounds were characterized by NMR spectroscopy, MS and elemental analysis. In addition, the molecular structures of the compounds were determined using DFT and X-ray (OPSf) analysis. The antibacterial activity of HSf and both derivatives was tested against four reference and fifteen clinical Gram-positive and Gram-negative strains of bacteria (sensitive or resistant to fluoroquinolones). The results showed that the activity of PSf was similar to or higher than the activity of HSf, while OPSf was found significantly less active. The compounds were also tested in vitro toward the following cancer cell lines: mouse colon carcinoma (CT26) and human lung adenocarcinoma (A549). Regardless of the cancer cell line, derivatization of HSf resulted in the gradual increase of cytotoxicity. OPSf exhibited the highest one (4 h – incubation time: IC50(CT26) = 51.0 ± 1.2; IC50(A549) = 74.9 ± 1.4 and 24 h: IC50(CT26) = 109.2 ± 8.8; IC50(A549) = 52.7 ± 9.2).

Graphical abstractTwo derivatives of sparfloxacin: aminomethyl(diphenyl)phosphine and its oxide were synthesized and characterized by NMR spectroscopy, MS and elemental analysis. Their molecular structures were determined using DFT and X-ray analysis. The phosphine oxide was found cytotoxic in vitro against CT26 and A549 cancer cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide