Phosphonate Conjugates and Bisphosphonate Platforms in Medicinal Chemistry: Prodrugs, Targeted Delivery, and Therapeutic Design

Phosphonate and bisphosphonate compounds are important structural motifs in medicinal chemistry due to their high chemical stability and their ability to mimic phosphate- and carboxylate-containing biological substrates. These features have supported their use in a range of therapeutic areas, including bone disorders, cancer, infectious diseases, and metabolic conditions. In recent years, growing attention has focused on phosphonate conjugates and bisphosphonate-based platforms as tools for prodrug development, targeted delivery, controlled release, and pharmacokinetic optimization. Their versatility makes them attractive for improving drug selectivity, tissue targeting, and therapeutic performance. At the same time, advances in synthetic methodologies, linker design, and biological evaluation are expanding the opportunities to tailor these compounds for specific pharmaceutical applications and clinically relevant therapeutic challenges.

This Research Topic aims to gather cutting-edge contributions on the design, synthesis, functionalization, and biological evaluation of phosphonate- and bisphosphonate-containing compounds for medicinal and pharmaceutical applications. The collection will provide a focused platform for studies exploring how these motifs can be used to improve drug delivery, enhance bioavailability, enable controlled release, and support rational therapeutic design.

Particular emphasis will be placed on prodrug strategies, targeted conjugates, scaffold modification, and structure–activity relationship studies that clarify the connection between molecular architecture and biological performance. The Topic also seeks to highlight translational approaches in which phosphonate- and bisphosphonate-based systems are developed for therapeutic use in areas such as oncology, bone-targeted therapy, infectious diseases, and metabolic disorders.

By bringing together researchers from medicinal chemistry, pharmaceutical sciences, chemical biology, and drug delivery, this collection aims to showcase innovative strategies that expand the therapeutic potential of phosphonate-based platforms and support future advances in drug development.

We welcome Original Research, Review, Mini Review and Perspective articles on themes including, but not limited to:
o Phosphonate and bisphosphonate scaffold design
o Prodrug strategies for phosphonate-based therapeutics
o Bone-targeted and tissue-selective conjugates
o Targeted delivery using phosphonate linkers
o Controlled release of phosphonate-containing agents
o Structure–activity relationships in phosphonate derivatives
o Pharmacokinetic optimization and bioavailability enhancement
o Anticancer applications of phosphonate platforms
o Anti-infective and antiparasitic phosphonate compounds
o Imaging and theranostic bisphosphonate systems
o Scaffold modification for selectivity and safety
o In vitro and in vivo therapeutic evaluation

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: Phosphonates, Bisphosphonates, Prodrugs, Targeted drug delivery, Medicinal chemistry

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.