Flavone-Based Anticancer Agents: Advances in Structure–Activity Relationships and Multitarget Mechanisms for Drug Design (2015–Present)
- 1Department of Chemistry, KwaDlangezwa Campus, University of Zululand, Empangeni 3886, South Africa
- 2College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa
Abstract
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.
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BibTeX
@article{mmonwa2026flavonebased,
title = {{Flavone-Based Anticancer Agents: Advances in Structure–Activity Relationships and Multitarget Mechanisms for Drug Design (2015–Present)}},
author = {Mmakwena M. Mmonwa and Malose J. Mphahlele},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213866},
url = {https://www.mdpi.com/1420-3049/31/21/3866},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Flavone-Based Anticancer Agents: Advances in Structure–Activity Relationships and Multitarget Mechanisms for Drug Design (2015–Present)
AU - Mmakwena M. Mmonwa
AU - Malose J. Mphahlele
PY - 2026
DA - 2026/10/27
JO - Molecules
DO - 10.3390/molecules31213866
UR - https://www.mdpi.com/1420-3049/31/21/3866
AB - 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.
SN - 1420-3049
ER -