Flavone-Based Anticancer Agents: Advances in Structure–Activity Relationships and Multitarget Mechanisms for Drug Design (2015–Present)

2-Phenylchromen-4-one–based compounds (e.g., flavones and flavonols) have emerged as privileged scaffolds in anticancer drug discovery owing to their ability to modulate multiple molecular targets involved in tumour initiation, progression, metastasis, angiogenesis, immune evasion, and therapeutic resistance. This review correlates key structural modifications or the structure–activity relationships (SARs) of the naturally occurring and synthetic flavone analogues to enhance anticancer activity across diverse molecular targets from 2015 till present. The influence of hydroxylation, methoxylation, halogenation, sulphur bioisosteric replacement, heterocyclic substitution, and hybridisation strategies on target affinity, selectivity, pharmacokinetics, and biological efficacy is critically discussed. Emphasis is placed on flavone core interactions with various targets, highlighting representative lead compounds and their biological activities. Recent advances in computational modelling, molecular docking, and hybrid drug design further demonstrate the value of SAR-guided optimisation for improving potency and overcoming drug resistance. Collectively, the evidence establishes flavones as versatile multitarget anticancer scaffolds and provides a rational framework for developing next-generation flavone-based therapeutics with improved efficacy, selectivity, and drug-like properties.