Rational Design of Newly Synthesized, Repurposed, and Nature-Isolated Biometabolites as Multi-Target Directed Ligands (MTDLs) for Cancer Treatment: Biological and Computational Approaches

Cancer continues to be a major cause of death globally, driven by complex genetic and molecular abnormalities that disrupt normal cell signaling and proliferation. Multi-target rational design in anticancer treatments is an advanced strategy that seeks to develop single molecules capable of modulating multiple oncogenic pathways, overcoming the limitations of single-target drugs, such as resistance, limited efficacy, and tumor heterogeneity. By integrating pharmacophoric features from different ligands or designing hybrid scaffolds, multitarget agents can achieve synergistic effects, enhance therapeutic outcomes, and reduce the need for combination therapy.

This Research Topic covers comprehensive insights regarding the rational design of multi-target-directed ligands (MTDLs) for cancer management, encompassing both biological and computational approaches. MTDLs offer a promising strategy to overcome the limitations of single-target drugs by simultaneously modulating multiple molecular pathways involved in cancer development and progression. This Research Topic focuses on the principles of MTDL design, including multi-target identification and selection, lead generation and optimization, and physicochemical property assessment. Additionally, it will highlight recent advances in computational methods for MTDL discovery, such as molecular docking, molecular dynamics simulations, and machine learning techniques. This discussion will also explore the potential of repurposing existing drugs and naturally-derived metabolites as multi-target-directed ligands (MTDLs), highlighting their advantages in safety, efficacy, and shorter development timelines. Current challenges, emerging trends, and future prospects in the field of MTDLs will also be examined, with emphasis on their impact on modern therapeutics. Furthermore, the role of late-stage functionalization of natural products and bioactive compounds—which has been crucial in developing MTDLs for therapeutic applications like cancer chemotherapy—will be highlighted.

We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
• Development, synthesis and biological evaluation of novel chemical entities such as MTDLs.
• Late-stage functionalization of natural products and bioactive compounds.
• Structural modifications of MTDLs for expanded understanding of their structure-activity relationships.
• Computational investigation for understanding insights regarding MTDLs’ pharmacokinetics and dynamics.
• Novel methodologies and technologies for application within drug discovery and development.

Article types and fees

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

• Editorial
• FAIR² Data
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

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

• Editorial
• FAIR² Data
• Mini Review
• Opinion
• Original Research
• Perspective
• Review

Keywords: Multi-target, Cancer, Rational design, Biology, Computational, Repurposing, Biometabolites, Late-stage functionalization

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.