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

Mihaela Lipovanu1, Anca Miron1, Nina Filip1

  • 1Grigore T. Popa University of Medicine and Pharmacy Iasi, 16, Universitatii Street, 700115 Iasi, Romania.

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|February 27, 2026
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Summary

Molecular hybridization of azoles and flavonoids creates novel anticancer drugs. These hybrids show enhanced potency, multitarget activity, and efficacy against resistant cancer cells, offering new therapeutic avenues.

Keywords:
anticancer activityazolesbreast cancer cellsflavonoidsleukemia cellsmolecular hybridizationselective cytotoxicitystructure–activity relationship

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Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Organic Synthesis

Background:

  • Cancer treatment faces challenges including limited efficacy, specificity, side effects, and drug resistance.
  • Molecular hybridization offers a strategy to overcome these limitations by combining multiple bioactive molecules.
  • Azoles and flavonoids are known for their individual anticancer properties, making them suitable candidates for hybridization.

Purpose of the Study:

  • To review the synthesis and anticancer potential of azole-flavonoid hybrids.
  • To highlight the advantages of these hybrids over existing therapies.
  • To discuss structure-activity relationships for optimized drug design.

Main Methods:

  • Comprehensive literature search for azole-flavonoid hybrids with reported anticancer activity.
  • Analysis of synthesized hybrids, focusing on triazole-chalcone, triazole-flavone, and other azole-flavonoid scaffolds.
  • Evaluation of reported antitumor potency, multitarget effects, cytotoxicity, and resistance profiles.

Main Results:

  • Over 250 azole-flavonoid hybrids have been synthesized and investigated.
  • Many hybrids exhibit superior antitumor potency compared to reference drugs.
  • These hybrids demonstrate multitarget activity, tumor-selective cytotoxicity, and efficacy against drug-resistant cancer cells.

Conclusions:

  • Azole-flavonoid hybrids represent a promising class of compounds for novel anticancer drug development.
  • Their multitargeting capabilities and effectiveness against resistant cells offer significant therapeutic potential.
  • Further research into structure-activity relationships can guide the design of more potent and selective anticancer agents.