Hybrid Compounds Containing a Ferrocene Scaffold as Potential Antimalarials

Malaria is an infectious disease, and it remains a serious health problem globally. The drugs developed for its treatment suffer from several shortcomings such as low water solubility, poor bioavailability, drug toxicity, and resistance. Molecular hybridization of different bioactive agents is a promising approach for developing hybrid compounds with improved therapeutic effects. Ferrocene, an organometallic, has been hybridized with several pharmacophores resulting in compounds with potent biological activities. In this research, a modified ferrocene scaffold was hybridized with selected pharmacophores. The synthesized compounds were characterized by Fourier-Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance Spectroscopy (NMR), and Liquid Chromatography-Mass Spectroscopy. The hybrid compounds were obtained in good yields (53-76 %). In vitro evaluation against NF54 (drug-sensitive) strain of Plasmodium falciparum parasites revealed the compounds, 16 and 19 (hybrids containing artesunate scaffold), together with 18 and 21 (hybrids containing oleanolic acid scaffold), as promising antimalarial agents. These compounds displayed IC50 values of 116.73 +/- 3.18, 56.33 +/- 15.20, 78.22 +/- 21.05, and 58.22 +/- 15.20 nM, respectively. These findings revealed the potency of ferrocene as a precursor for the development of promising antimalarials.

Automated summary

Malaria remains a serious global health issue, with drug development facing challenges such as low solubility and resistance. Hybrid compounds through molecular fusion of bioactive agents show promise in improving therapeutic effects. This study demonstrates the potential of ferrocene as a precursor for developing promising antimalarials, with synthesized compounds showing efficacy against Plasmodium falciparum parasites.