Rational Design and Anticancer Mechanisms of Organometallic Complexes Targeting Tumor-Specific Pathways

Organometallic complexes represent an important class of compounds with high potential as anticancer agents in modern medicinal chemistry, owing to their structural diversity, tunable chemical properties, and strong biological activity. The presence of a metal center enables precise control over geometry and coordination properties, expanding their interactions with biomolecules and supporting innovative anticancer strategies. In particular, these compounds can target cancer-relevant biomolecular pathways, including DNA damage and redox homeostasis, thereby disrupting replication and transcription processes and inducing cancer cell death. Binding to serum albumin is also important for their pharmacokinetic behavior, affecting stability, transport, and bio-distribution, and contributing to their in vivo performance. Notably, organometallic complexes may exhibit selective activity toward cancer cells by exploiting their altered metabolism and proliferative capacity compared to normal tissues. Current research increasingly focuses on the rational design of such compounds and the elucidation of their mechanisms of action, correlating structure with biological activity and biomolecular interactions to develop more selective and effective anticancer agents with translational potential.

The development of organometallic complexes as anticancer agents is challenged by an incomplete understanding of their structure–activity relationships and mechanisms of action at the molecular and cellular levels. Although numerous compounds exhibit significant cytotoxic effects, their precise biological targets, signaling pathways, and impact on tumor-specific processes are often insufficiently characterized, limiting further optimization and potential preclinical development. In addition, a lack of detailed insight into their interactions with key biomolecules, such as DNA and serum albumins, complicates the prediction of their stability, transport, and bioavailability under physiological conditions.

The goal of this Research Topic is to address these challenges by integrating rational design with comprehensive biological evaluation of organometallic complexes in relevant cancer models. Particular emphasis will be placed on the investigation of cytotoxic activity against tumor cell lines, alongside detailed studies of their mechanisms of action, including apoptosis induction, cell cycle modulation, oxidative stress responses, and other cancer-associated pathways. Furthermore, understanding interactions with DNA and transport proteins will provide valuable information on their molecular behavior and pharmacokinetic properties. Recent advances in spectroscopic methods, molecular modeling, and in vitro and in vivo techniques offer powerful tools to achieve these aims. By integrating these approaches, this Research Topic seeks to contribute to the development of more effective, selective, and mechanistically understood organometallic anticancer agents.

We welcome Original Research, Review, Mini Review, and Perspective articles on themes including, but not limited to:

- Rational design and synthesis of organometallic complexes with demonstrated anticancer activity
- In vitro and in vivo cytotoxicity studies in relevant cancer models
- DNA and serum albumin binding studies in the context of anticancer activity and pharmacokinetics
- Mechanistic studies including apoptosis induction, cell cycle arrest, oxidative stress, and other cancer-related pathways
- Structure–activity relationship (SAR) analysis of organometallic anticancer agents
- Computational approaches including molecular docking and molecular dynamics simulations in biologically relevant systems

Please note: manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this Research Topic.

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This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Organometallic complexes, DNA/serum albumin interaction, cytotoxicity, molecular docking

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.