ANTIMICROBIAL AND ANTICANCER POTENTIAL OF [FE(BIPY)3][(U-OXO)FE2CL6]

Abstract

ABSTRACT OF THE INVENTION The present invention relates to a novel mixed valence iron complex, [Fe(bipy)3][(p- oxo)Fe2Cl6], with significant potential for therapeutic applications, specifically in microbial inhibition and anticancer treatments. The invention includes the comprehensive structural characterization of the complex, confirmed by infrared (IR.) spectroscopy, ultraviolet-visible (UV-Vis) spectroscopy, and single crystal X-ray diffraction, which elucidate the geometry and electronic structure of the compound. The invention further explores the biological efficacy of the complex, demonstrating potent antimicrobial activity against Staphylococcus aureus, Candida albicans, Streptococcus mutans, and Enterococcus faecal is, as evidenced by disk diffusion tests and minimum inhibitory concentration (MIC) measurements. The complex also exhibits pronounced anticancer properties, as evaluated by the MTT assay on the KB celMine, indicating its potential as an.. effective, therapeutic agent. .Moreover,, the complex shows promising anti-biofilm activity, highlighting its multifaceted applicability in the development of novel therapeutic interventions. This invention is therefore directed toward the use of [Fe(bipy)3][(p-oxo)Fe2Cl6] in pharmaceutical compositions for the treatment of microbial infections and cancer.

Specification

The present invention relates to the field of medicinal chemistry, specifically to the development, synthesis, and therapeutic applications of mixed valence iron complexes, particularly . [Fe(bipy)3][(p-oxo)Fe2Cl6], with potential antimicrobial and anticancer
properties.


BACKGROUND OF THE INVENTION:
The development of novel metal complexes has attracted considerable interest in medicinal chemistry due to their potential applications in antimicrobial and anticancer therapies [1]. Among these, mixed valence iron complexes have emerged as promising candidates, primarily due to their unique electronic properties and versatile coordination chemistry [2]. Within this framework, the mixed valence iron complex with amine ligands represents a compelling area of investigation [3]. These complexes not only exhibit distinctive structural characteristics but also provide opportunities for fine-tuning their biological activity by modifying the ligand environment. Additionally, the incorporation of amine ligands enhances the stability and solubility of these complexes, further amplifying their therapeutic potential.
The complex [Fe(phen)3][(p-oxo)Fe2Clfi] is particularly notablefor its structural __ features, where 1,10-phenanthroline (phen) serves as a ligand, stabilizing the iron centers in varying oxidation states [4]. The p-oxo bridge between the iron centers is essential for maintaining the stability and electronic configuration of the complex. A thorough understanding of the geometry and electronic structure of these complexes is crucial for elucidating their biological activities [5]. The specific arrangement of iron centers and the bridging oxygen atom significantly influences the reactivity and interaction of the complex with biological molecules, thereby playing a crucial role in its antimicrobial and anticancer
properties [6].
The potential of mixed valence iron complexes with a bridging oxygen atom in biomedical applications is further supported by their promising antimicrobial and anticancer properties [7], The rising incidence of multidrug-resistant microbial strains and the ongoing demand for effective cancer treatments highlight the importance of exploring new therapeutic agents [8]. Previous studies have suggested that metal complexes can exhibit enhanced biological activity due to their interactions with biomolecules through various mechanisms, including DNA binding, enzyme inhibition, and the generation of reactive oxygen species [9J. These interactions can disrupt cellular processes in pathogens and cancer cells, positioning such complexes as potent candidates for novel therapeutic strategies.
In this context, the present study aims to investigate the structural and biological properties of [Fe(bipy)3][(p-oxo)Fe2C16]. Comprehensive structural characterization will be conducted using FTIR, UV-Vis, and single crystal X-ray diffraction techniques to provide detailed insights into the geometry and electronic structure of the complex. The biological potential of this complex will be evaluated through antimicrobial and anticancer assays.


Specifically, the anticancer activity will be assessed using the MTT assay on the oral cancer KB cell line, while its antibacterial efficacy will be tested against common pathogens such as Staphylococcus aureus,. Candida albicans, Streptococcus mutans, and Enterococcus faecalis using disk diffusion and minimum inhibitory concentration (MIC) methods. By elucidating the. structural characteristics and biological activities of [Fe(bipy)3][(p-oxo)Fe2Cle], this study aims to contribute to the.development of new therapeutic agents with potential applications in combating microbial infections and cancer.


BRIEF DESCRIPTION OF THE PRODUCT:
The product is a novel iron bipyridine complex, [Fe(bipy)3][(p-oxo)Fe2Cl6], whose structural characterization and biological activities have been thoroughly investigated using FT1R, UV- vis spectroscopy, and Single Crystal XRD, The oxide bridge within the complex significantly enhances its structural stability, contributing to its potent antimicrobial and anticancer properties. The complex exhibits strong antibacterial activity, with mechanisms likely involving disruption of bacterial cell walls, interference with protein functions, and generation of reactive oxygen species, and is notably effective in inhibiting biofilm formation, achieving up to 92% reduction in biofilm biomass at higher concentrations.
Additionally, the complex demonstrates considerable cytotoxicity against oral cancer KB cell lines, with up to 91% cell death observed at higher concentrations. These promising findings suggest.potential applicationsJn antimicrobial-therapies and-cancer treatments,-though further- research is necessary to optimize its therapeutic efficacy.


DETAILED DESCRIPTION OF THE INVENTION:
The detailed structural characterization of iron bipyridine complexes offers profound insights into their coordination chemistry and electronic properties, employing techniques such as FTIR, UV-vis electronic spectroscopy, and Single Crystal XRD. The coordination environment and precise bond lengths within the mixed-valence complex, particularly the presence of the oxide bridge in [Fe(bipy)3][(p-oxo)Fe2Cl6], play a pivotal role in enhancing both the structural stability and the electronic configuration of the complex, which are essential to its biological activity. These structural features not only contribute to the complex's stability but also suggest potential mechanisms underlying its antimicrobial and anticancer properties, making it a promising candidate for therapeutic applications.
In antimicrobial contexts, the title complex shows significant potential for treating bacterial infections, surpassing the activity of.previously reported monomeric complexes. Its potent antibacterial effects may stem-from the unique combination of the bipyridine ligand, the mixed-valence iron center, and the oxide bridge, which together may disrupt bacterial cell wall synthesis, interfere with protein functions, or generate reactive oxygen species. The evaluation of its antibiofilm activity across various bacterial strains, using the crystal violet assay, revealed a concentration-dependent inhibition of biofilm formation. At a concentration of l.O mM, the title complex achieved a 92% reduction in biofilm biomass, demonstrating robust antibiofilm activity. Even at lower concentrations, the complex caused a substantial decrease in biofilm formation, suggesting multiple mechanisms through which it disrupts biofilm integrity, including the destabilization of the biofilm matrix by the bipyridine ligand and the mixed-valence iron ion.
The anticancer potential of the title iron complex was assessed using the MTT assay on oral cancer KB cell lines across various concentrations, with a focus on its effects over a 24-hour period. While lower concentrations initially appeared to increase cell viability and proliferation, higher concentrations revealed marked cytotoxicity. Notably, the complex induced 80% cytotoxicity at 100 pg/mL and 91% cytotoxicity at 150 pg/mL. Cells treated with 80 pg/mL of the complex for 24 hours displayed 53% cytotoxicity compared to the control group, with corresponding dose-dependent morphological changes observed under phase-contrast microscopy. These findings highlight the significant cytotoxic effects of the title iron complex, underscoring the need for careful dosage optimization to maximize anticancer efficacy while minimizing adverse effects.
Moreover, the complex's ability to induce apoptosis and its potential for use in combination therapies point to promising avenues for the development of more effective and


safer cancer treatments. These findings emphasize the importance of continued research to refine the formulation and dosage of the title iron complex, ensuring that it delivers maximum therapeutic benefits in both antimicrobial and anticancer applications. The novel structure and activity of this complex open new possibilities for advancing therapeutic strategies against resistant bacterial strains and aggressive cancer types


SUMMARY OF THE INVENTION:
The present invention pertains to the innovative mixed valence iron complex [Fe(bipy)3][(p-oxo)Fe2Cl6], which has been comprehensively evaluated for its structural and biological properties, demonstrating significant potential as a versatile therapeutic agent.
Detailed structural characterization using IR, UV-Vis, and single crystal X-ray diffraction has elucidated the geometry and electronic structure of the complex, which features a bipyridine ligand, mixed valence iron, and an oxygen bridge. The invention includes claims related to the complex's antimicrobial efficacy, where it has shown superior antibacterial activity against gram-positive bacterial strains, surpassing standard antibiotics. Additionally, the complex exhibits strong antibiofilm properties, effectively disrupting biofilm integrity at low concentrations,. an important feature for overcoming bacterial resistance. In anticancer applications, the complex has demonstrated substantial cytotoxicity against oral cancer KB cells in a dose-dependent manner, attributed to its ability to induce oxidative stress and apoptosis. The invention highlights the therapeutic potential of [Fe(bipy)3][(p-oxo)Fe2Cl6] as an antimicrobial, antibiofilm, and anticancer agent, with further research recommended to optimize its formulation and explore the underlying mechanisms of its action for safer and more effective treatments.


CLAIMS
28-Oct-2024/130613/202441082038/Form 2(Title Page)
1. A pharmaceutical composition comprising [Fe(bipy)3][(p-oxo)Fe2Cl6]: This claim pertains to a pharmaceutical composition in which the mixed valence iron complex [Fe(bipy)3][(p-oxo)Fe2CU] is included as the active ingredient, designed for antimicrobial and anticancer therapeutic applications. 2. A method of synthesizing [Fe(bipy)3][(p-oxo)Fe2Cl6]: This .claim describes a method for synthesizing the mixed valence iron complex [Fe(bipy)3][(p-oxo)Fe2Cl6], with particular emphasis on the process steps required to form the p-oxo bridge and stabilize the iron centers in various oxidation states. 3. A 'method of inhibiting microbial growth using [Fe(bipy)3][(p-oxo)Fe2Cl6]: This claim covers a method for inhibiting the growth of bacterial and fungal pathogens, specifically Staphylococcus aureus, Candida albicans, Streptococcus mutans, and Enterococcus faecalis, by administering [Fe(bipy)3][(p-oxo)Fe2Cl6]. 4. An application of [Fe(bipy)3][(p-oxo)Fe2Cl6] in anticancer therapy: This claim involves the application of the mixed valence iron complex [Fe(bipy)3][(p- oxo)Fe2Cl6] as an anticancer agent, focusing on its effectiveness in inhibiting the proliferation of cancer cells, particularly in oral cancer cell lines. 5. A method for enhancing the stability and solubility of mixed valence iron complexes: This claim is directed toward a method of enhancing the stability and solubility of mixed valence iron complexes, such as [Fe(bipy)3][(p-oxo)Fe2Cl6], through the incorporation of amine ligands, thereby improving their therapeutic efficacy in biomedical applications.

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