Synthesis, Characterization, Crystal Structures and Urease Inhibition of Thiosemicarbazones.

Area of Science:

• Medicinal Chemistry
• Biochemistry
• Structural Biology

Background:

• Thiosemicarbazones are a class of biologically active compounds with diverse pharmacological properties.
• Urease is a crucial enzyme implicated in various pathological conditions, making it a target for therapeutic intervention.

Purpose of the Study:

• To synthesize and structurally characterize novel thiosemicarbazone derivatives.
• To evaluate the urease inhibitory potential of these newly synthesized compounds.
• To investigate the binding interactions of active compounds with urease through molecular docking.

Main Methods:

• Synthesis of six new thiosemicarbazone compounds.
• Structural elucidation using elemental analysis, 1H NMR, IR spectroscopy, and single crystal X-ray diffraction.
• In vitro evaluation of urease inhibitory activity (IC50 determination).
• Molecular docking simulations against the crystal structure of Jack bean urease.

Main Results:

• Successful synthesis and full characterization of six novel thiosemicarbazones.
• Identification of potent urease inhibitors among the synthesized compounds, particularly those bearing hydroxyl and chlorine substituents.
• Achieved IC50 values ranging from 1.8 to 12.7 μmol∙L-1 for the most active compounds.
• Molecular docking studies provided insights into the probable binding modes within the urease active site.

Conclusions:

• The synthesized thiosemicarbazone derivatives, especially those with hydroxyl and chlorine groups, exhibit significant urease inhibitory activity.
• These findings highlight the potential of these compounds as lead structures for developing new urease inhibitors.
• Further studies are warranted to explore their therapeutic applications and optimize their inhibitory profiles.