Heteroleptic Transition Metal Complexes of Eflornithine Hydrochloride Monohydrate: Synthesis, Characterization, in silico and in vitro Biological Studies

Abstract

Incessant development of resistance to drugs by microorganisms remains a major setback associated with the currently available antibiotics, thereby making imperative a continuous search for alternative candidates with improved efficacy. Previous studies have shown enhanced antimicrobial activity of some bioactive molecules upon coordination with metal ions. Thus, in this study, Cu(II), Co(II), and Ni(II) complexes of eflornithine hydrochloride monohydrate (EHM) were synthesized and probed for bactericidal activity via in vitro and in silico. The characterization results such as CHN analysis, FTIR, UV-visible magnetic susceptibility and Electrospray Ionization Mass Spectrometry (ESI-MS) reveal that EHM coordinates as a bidentate ligand to each central metal ion in the molar ratio 1:2 through O and N in the COO- and NH2 group respectively, and also suggest octahedral geometry in each complex. The physicochemical and pharmacokinetics parameters predicted in silico support the bio-applicability and safety of the complexes. From the in vitro antibacterial study, the complexes demonstrate improved activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa with an average minimum inhibitory concentration (MIC) of 0.01 mg/L similar to ciprofloxacin, compared to EHM whose MIC >1.00 mg/L. Although, not all the complexes satisfy Lipinski’s drugability rule of 5 due to their molecular weight, however, coordination with metal ions improves the biological activities of EHM and the complexes demonstrate potential for further transformation into antibiotic therapeutics.

Keywords

• Bioinorganic coordination chemistry
• antibiotics
• gram positive and negative bacteria
• eflornithine
• drug resistance

Thanks

The authors gratefully acknowledge the financial support from the World Bank Science and Technology Education Post-Basic Project (STEP-B) TETFUND, Department of Chemistry University of Ilorin, Nigeria and also Tetfund Nigeria for PhD scholarship awarded to YOA.

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