Josiah, Andrea JGovender, KKGovender, PPRay, Suprakas S2024-11-212024-11-212025-082513-0390https://doi.org/10.1002/adts.202400377http://hdl.handle.net/10204/13832This review highlights the role of computational chemistry, specifically quantum and molecular mechanics, in the development of folate-based anticancer drugs. Folate receptors (FRs) are overexpressed in cancerous cells, rendering these receptors a key focus in the design of targeted drug delivery systems. These computational tools are fundamental for analyzing drug–receptor interactions and overcoming the limitations of traditional drug development processes. A 10-year literature survey demonstrated advancements in employing FRs for targeted cancer therapy. Key findings reveal that structural modifications to folate derivatives consistently enhance binding affinities and specificity toward FRα and FRβ. Computational methodologies predicted and analyzed molecular interactions, validated by experimental data. Functional groups play a crucial role in enhancing binding stability and interaction strength within FR binding pockets. Detailed structural insights into folate derivatives and antifolates interacting with FRs have identified critical residues involved in binding, aiding the design of targeted therapeutics.FulltextenFolate-based anticancer drugsComputational chemistryDrug-receptor interactionsAnticancer drugsArticleN/A