Ferrocene-based guanidine derivatives: In vitro antimicrobial, DNA binding and docking supported urease inhibition studies

• New ferrocenyl guanidine derivatives were synthesized.
• The new compounds 1–3 displayed significant antifungal activity against Aspergillus flavus.
• The DNA-binding propensity was investigated by UV–vis and CV techniques.
• Compound 1 demonstrated a significant activity against Jack bean urease.
• A molecular docking study of all the compounds with the urease enzyme was performed.

Some novel ferrocenyl guanidines 1–8 were synthesized and characterized by different spectroscopic methods, elemental analysis and single crystal X-rays diffraction techniques. The crystallographic studies revealed that the existence of the strong non-bonding interactions facilitate these molecules to interact with biological macro-molecules like DNA that described to inherit good biological activities. The DNA interaction studies carried out by cyclic voltammetry (CV) and UV–visible spectroscopy are in close agreement with the binding constants (K) (0.79–5.4) × 105 (CV) and (0.72–5.1) × 105 (UV–vis). The shift in peak potential, current and absorption maxima of the studied ferrocenyl guanidines in the presence of DNA revealed that CV coupled with UV–vis spectroscopy could provide an opportune to characterize metal-based compounds–DNA interaction mechanism, a prerequisite for the design of new anticancer agents and understanding the molecular basis of their action. The compounds 1–8 have been screened for their antibacterial, antifungal and urease inhibition potency. A concurrent in silico study has also been applied on ferrocene moiety impregnated guanidines 1–8 to identify most active compounds having for inhibiting the activity of urease (pdb id 3LA4). Most of the compounds were found as potent inhibitors of urease and the compound 1 was found to be the most active with an IC50 of 16.83 ± 0.03 μM. The docking scores are in close agreement with the in vitro obtained IC50 values of inhibitors 1–8.

The variation in peak potentials and current intensities in CV (II) and the wavelength shifts in UV–vis (I) supporting the interaction of (1) with urease metalo-enzyme (PDB-ID 3LA4) (III).Figure optionsDownload as PowerPoint slide