Exploring the Synthetic Chemistry of Phenyl-3-(5-aryl-2-furyl)- 2-propen-1-ones as Urease Inhibitors: Mechanistic...

Area of Science:

• Medicinal Chemistry and Pharmacology
• Organic Synthesis and Heterocyclic Chemistry

Background:

• Furan chalcones are privileged oxygen-containing heterocyclic compounds with diverse therapeutic applications.
• Bacterial urease enzymes are significant targets for developing antimicrobial and anti-ulcer agents.

Purpose of the Study:

• To synthesize novel furan chalcone analogues using microwave-assisted and conventional methods.
• To evaluate the synthesized compounds for their potential as bacterial urease enzyme inhibitors.

Main Methods:

• Synthesis of 19 substituted 5-aryl-2-furan-2-carbaldehyde derivatives via Claisen-Schmidt condensation.
• Microwave-assisted and conventional synthesis of 19 furan chalcone scaffolds.
• Characterization using elemental analysis and spectroscopic techniques; evaluation of urease inhibitory activity.

Main Results:

• Successful synthesis of 19 furan chalcone derivatives in good to excellent yields.
• Compounds 4h (1-phenyl-3-[5-(2',5'-dichlorophenyl)-2-furyl]-2-propen-1-one) and 4s (1-phenyl-3-[5-(2'-chlorophenyl)-2-furyl]-2-propen-1-one) showed potent urease inhibition (IC50 values of 16.13 ± 2.45 μM and 18.75 ± 0.85 μM, respectively).
• These compounds exhibited superior activity compared to the reference drug thiourea (IC50 = 21.25 ± 0.15 μM).

Conclusions:

• Furan chalcone derivatives, particularly those with 2,5-dichloro and 2-chloro moieties, are effective urease inhibitors.
• The findings support the potential of these furan chalcones as lead compounds for developing novel urease inhibitory agents.
• In silico molecular docking studies corroborated the experimental biological activity.