# Azole–Flavonoid Hybrids as Emerging Anticancer Agents: A Bioactivity-Focused Review

## TL;DR

This review explores azole–flavonoid hybrids as promising new anticancer drugs with improved effectiveness and reduced resistance.

## Contribution

The paper systematically reviews 250 azole–flavonoid hybrids and their anticancer potential, emphasizing their multitarget activity and tumor selectivity.

## Key findings

- Azole–flavonoid hybrids show superior antitumor potency compared to traditional reference drugs.
- These hybrids demonstrate efficacy against drug-resistant tumor cells and exhibit multitarget activity.
- Structure–activity relationships are highlighted to guide future drug development.

## Abstract

Despite notable progress in drug discovery, cancer treatment remains hindered by limited therapeutic efficacy, poor target specificity, adverse effects, and the development of drug resistance. Molecular hybridization, which integrates two or more bioactive entities into a single molecule, has shown considerable potential to overcome these limitations. Since both azoles and flavonoids have demonstrated anticancer potential, extensive studies have been undertaken to combine the two entities and enhance the bioactivity of the resulting hybrids. In this context, numerous azole–flavonoid hybrids have been synthesized and investigated for their anticancer potential. This review provides an overview of the azole–flavonoid hybrids that are promising candidates for novel anticancer drug development, highlighting their superior antitumor potency compared to reference drugs, multitarget activity, tumor-selective cytotoxicity, efficacy against drug-resistant tumor cells, and structure–activity relationships. The review covers 250 hybrids, primarily triazole–chalcone hybrids but also triazole–flavone, flavanone, flavonol, and isoflavone hybrids, as well as other azole–flavonoid hybrids (imidazole–, pyrazole–, isoxazole–, and thiazole–flavonoid hybrids).