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Exploring chalcone-based azo dyes as potential carbonic anhydrase-I/II inhibitors through experimental and
Ehsan Ullah Mughal1, Nafeesa Naeem1, Ishtiaq Ahmed2
1Department of Chemistry, University of Gujrat, Gujrat 50700, Pakistan.
Bioorganic Chemistry
|July 9, 2026
Summary
New azo-chalcone derivatives show potent inhibition of carbonic anhydrases (CAs), enzymes crucial for various physiological processes. Compound 1 is a promising lead for developing novel CA inhibitors for conditions like glaucoma and cancer.
Area of Science:
- Medicinal Chemistry
- Enzymology
- Pharmacology
Background:
- Carbonic anhydrases (CAs) are vital zinc metalloenzymes implicated in numerous physiological functions.
- Dysregulation of CA activity is linked to diseases including glaucoma, epilepsy, and cancer, making them key therapeutic targets.
Purpose of the Study:
- To design, synthesize, and evaluate novel azo-linked chalcone derivatives as inhibitors of human carbonic anhydrase isoforms I and II (hCA I and hCA II).
- To identify potent lead compounds for further development as therapeutic agents.
Main Methods:
- Synthesis of a series of ten azo-linked chalcone derivatives.
- In vitro enzymatic assays to determine inhibitory activity against hCA I and hCA II.
- Structure-activity relationship (SAR) analysis.
- Molecular docking and molecular dynamics (MD) simulations.
- In silico ADMET profiling for pharmacokinetic assessment.
Main Results:
- All synthesized compounds exhibited potent inhibition against hCA I and hCA II in the low nanomolar range.
- Compound 1 demonstrated superior inhibitory activity, particularly against hCA II, outperforming the reference drug acetazolamide.
- SAR analysis revealed the importance of the azo-linked aromatic moiety and chalcone substitution patterns for activity.
- Molecular modeling studies confirmed favorable binding interactions and acceptable pharmacokinetic properties, suggesting good drug-likeness.
Conclusions:
- Azo-chalcone hybrids represent a promising scaffold for developing effective carbonic anhydrase inhibitors.
- Compound 1 is identified as a strong preclinical candidate for further optimization and investigation.
- These findings support the therapeutic potential of novel azo-chalcone derivatives for CA-related disorders.
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