Ferrocene-functionalized anilines as potent anticancer and antidiabetic agents: Synthesis, spectroscopic elucidation, and DFT calculations

Abstract

Ferrocene derivatives have attracted significant interest as potent biological agents and novel drug candidates. Hence, the present research work was focused on the synthesis and characterization of ferrocene-integrated anilines (FB1-FB4) through different spectroscopic techniques such as: FT-IR, multinuclear (1H and 13C) NMR, Raman, atomic absorption spectroscopy, elemental analysis, and single-crystal X-ray crystallography. The crystallographic analysis revealed a supramolecular structure mediated by secondary non-covalent interactions (π—H and π—π). These ferrocenyl derivatives demonstrated a quasi-reversible electrochemical behavior with one electron transfer from Fe(II) to Fe(III)., which was evident by the change in the peak potential at different scan rates. The theoretically calculated energies of the HOMO-LUMO orbitals and the Mulliken charge distribution for the optimized structures determined by the DFT/B3LYP method associated well with the electrochemically measured redox potentials. The computational measurements also led to a close agreement between the found and observed vibrational frequencies having a correlation coefficient of 0.999. The in silico docking analysis against α-amylase, urease, and tyrosine kinase revealed that the docking scores are in close agreement with the in vitro obtained IC50 values of inhibitors. The synthesized compounds exhibited notable free radical scavenging activity against DPPH with IC50 values between 15.9–31.5 µM. The anticancer activity data revealed modest cytotoxicity against the subjected cancer cell line (MCF-7) compared with standard chemotherapeutic drug (cisplatin). However, these ferrocenyl analogs had fewer toxic effects in normal cells (MCF-10A). The results of the antidiabetic assay established that FB1 (IC50 = 19.27 µg/mL) is potentially more active inhibitor of α-amylase, the theoretical docking studies stating that FB1 is more prone towards hydrophobic interactions with Leu165 and Trp 59, in the active pocket of alpha-amylase. Together, the current study reveals the anti-cancer, anti-diabetic and anti-oxidant potential of newly synthesized ferrocene-substituted anilines.