Synthesis and characterization of hybrid compounds containing ferrocene scaffold as potential anticancer drugs
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Date
2024-11
Authors
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Publisher
University of Fort Hare
Abstract
Cancer is one of the diseases, and its treatment suffers from several limitations. For instance, there are several commercially available drugs to treat this lethal disease. However, they still display shortcomings such as drug toxicity and resistance, poor water solubility, poor bioavailability, and severe side effects. Thus, their efficacy is compromised by these limitations. The emerging drug repurposing strategy is gaining momentum from medicinal researchers. This comes after several compounds have been reported to possess various biological activities. Thus, the hybridization approach via drug reprofiling has been an interesting field of research. Hence, this study reports the synthesis of hybrid compounds as potential anticancer drugs. Two ferrocene scaffolds (ferrocene and ferrocene carboxaldehyde) were modified to keto-ferrocene butanoic acid (16) and methyl-ferrocenol (18) and hybridized with several selected pharmacophores via esterification and amidation reactions using suitable functional groups, resulting in a class of eleven esterlinked (19-29) and five amide-linked (30 34) hybrids. The characterization techniques including Fourier Transform Infrared (FTIR) spectroscopy, Nuclear magnetic resonance (NMR) spectroscopy, and Liquid chromatography mass spectrometry (LC-MS) confirmed the successful development of these hybrids by displaying the expected signals at the expected regions of the spectra.
Most importantly, the molecular weights calculated corresponded with those obtained by the LCMS on the samples. In vitro, two hybrid compounds, 20 ( thymol-keto-ferrocene butanoate) and 27 (ursolic-ferrocenoate), were the most promising anticancer compounds, displaying a 50% cytotoxic effect against cervical cancer (HeLa) and Chinese hamster ovary (CHO) cell lines and less than 20% on normal cells (VERO). Noteworthy, the cytotoxicity was concentrationdependent. Furthermore, hybrid 20 was the most effective compound with a selective index greater than one from the series. Thus, the findings from the molecular docking of these two most promising hybrids further confirmed the in vitro findings, which revealed high negative docking scores, signifying binding interactions and good binding affinity of the compounds towards the biological targets. The in silico predictions of the two also showed they are non-toxic, have a good bioavailability score (0.55<), are P-gp substrates, and do not inhibit most of the CPY enzymes. Hence, this study reveals the efficacy of synthesizing hybrid compounds containing ferrocene scaffolds and plant-based pharmacophores, such as thymol and ursolic acid. Developing hybrid molecules is a promising synthetic approach for potent anticancer agents.
Description
PhD in Chemistry
Keywords
Antineoplastic agents, Ferrocene, Organometallic compounds, Drugs -- Design, Cancer -- Chemotherapy
Citation
Peter, S. (2024) Synthesis and characterization of hybrid compounds containing ferrocene scaffold as potential anticancer drugs. PhD thesis. Alice, South Africa: University of Fort Hare.