Ciprofloxacin/Topoisomerase-II complex as a promising dual UV–Vis/fluorescent probe: accomplishments and opportunities for the cancer diagnosis

In this work, a dual UV–Vis/fluorescent probe to be used in cancer diagnosis is proposed by theoretical investigations of the interaction of ciprofloxacin (CPX) molecule with human Topoisomerase-II β enzyme, and its respective excited state properties. Molecular docking simulations suggest that CPX has similar inhibitory effects for human and bacteria Topoisomerase-II, and for human enzyme, CPX interacts preferentially in the same site of chemotherapeutic etoposide (EVP). In TD-DFT parametrization for CPX, it was found that Global Hybrid functionals containing around 25% of exact exchange contribution, such as mPW1PW91, M06 and PBE0, are most suitable for computing excitation energies for CPX. Also, explicit solvent model calculations allow results closer to the real. For excited state properties, theoretical calculations show that there are changes in absorption energy of CPX, and the distance between Tyrosine 821 residue of human enzyme and CPX can also enable a Fluorescence resonance energy transfer (FRET) between the two molecules. Therefore, it is suggested in this work that both the variation in the absorption energy of the CPX (UV–Vis spectra) and the variation in the excitation energy of Tyr (821) (Fluorescence spectra) can be used in a dual-sensor to monitor the overexpression of hTOPO-II, constituting a promising tool in cancer diagnosis.