The Role of Density Functional Theory in the Design and Analysis of Heterocyclic Anticancer Agents: A Comprehensive Review
Khawlah Ahmad Alzenaidi, Mohamed N. El‐Bayaa, Sabri Messaoudi · JOURNAL of QASSIM UNIVERSITY FOR SCIENCE · 2026
Density Functional Theory (DFT) has emerged as an indispensable computational tool in modern drug discovery, particularly in the design and optimization of heterocyclic compounds as anticancer agents. This comprehensive review synthesizes current applications of DFT across diverse heterocyclic scaffolds, examining its role in structural characterization, electronic property prediction, mechanistic elucidation, and rational drug design. We analyzed studies demonstrating how simulations and inform structure-activity relationships (SAR), predict binding affinities through integration with molecular docking and dynamics simulations, and guide the development of novel therapeutics. Special emphasis is placed on frontier molecular orbital (FMO) analysis, reactivity descriptors, spectroscopic correlations, and the synergistic integration of DFT with experimental techniques. This review highlights DFT’s transformative impact on heterocyclic anticancer drug development and identifies future directions for computational medicinal chemistry.