Hybrid Compounds Containing a Ferrocene Scaffold as Potential Antimalarials

Abstract

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.

Natural products and drug discovery

“…There was also some selectivity demonstrated on assaying them against human normal and tumor cells. These compounds still need further refinement but aptly demonstrate that such molecules have potential [ 14 , 15 ], with examples discussed in the next section.…”