Academic Journal

Synthesis of thiosemicarbazone derivatives of thiophene-2-carboxylic acid as potent urease inhibitors: in vitro evaluation, molecular docking, and density functional theory analysis.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Synthesis of thiosemicarbazone derivatives of thiophene-2-carboxylic acid as potent urease inhibitors: in vitro evaluation, molecular docking, and density functional theory analysis.
Συγγραφείς: Khan W; Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan., Laiba; Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan., Ahmad I; Programa de Pós-Graduação em Bioquímica e Bioprospecção, Universidade Federal de Pelotas, Pelotas, Brazil., Elhenawy AA; Chemistry Department, Faculty of Science, Al-Azhar University, Cairo, Egypt., Shah SAA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam Campus, Bandar Puncak Alam, Malaysia.; Atta-ur-Rahman Institute for Natural Product Discovery (AuRIns), Universiti Teknologi MARA Cawangan Selangor Kampus Puncak Alam, Bandar Puncak Alam, Malaysia., Alanazi AS; Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia., Shakoor A; Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan., Alam A; Department of Chemistry, Rawalpindi Women University, Rawalpindi, Pakistan., Khan M; Department of Chemistry, Abdul Wali Khan University, Mardan, Pakistan., Alanazi MM; Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Πηγή: Future medicinal chemistry [Future Med Chem] 2026 Aug; Vol. 18 (16), pp. 2147-2159. Date of Electronic Publication: 2026 Jul 13.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Taylor & Francis Country of Publication: England NLM ID: 101511162 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1756-8927 (Electronic) Linking ISSN: 17568919 NLM ISO Abbreviation: Future Med Chem Subsets: MEDLINE
Imprint Name(s): Publication: 2024- : [Milton Park, Oxfordshire] : Taylor & Francis
Original Publication: London : Future Science, 2009-
Ιατρικοί όροι (MeSH): Urease*/antagonists & inhibitors , Urease*/metabolism , Enzyme Inhibitors*/chemical synthesis , Enzyme Inhibitors*/chemistry , Enzyme Inhibitors*/pharmacology , Thiosemicarbazones*/chemistry , Thiosemicarbazones*/chemical synthesis , Thiosemicarbazones*/pharmacology , Thiophenes*/chemistry , Thiophenes*/pharmacology , Thiophenes*/chemical synthesis , Density Functional Theory*, Molecular Docking Simulation ; Structure-Activity Relationship ; Molecular Structure ; Molecular Dynamics Simulation ; Carboxylic Acids
Περίληψη: Aims: To synthesize and evaluate a series of thiosemicarbazone derivatives (2a-2g) incorporating thiophene-2-carboxylic acid as urease inhibitors.
Materials and Methods: The compounds were synthesized and characterized using modern spectroscopic techniques. In vitro urease inhibition was determined followed by computational analysis including docking, density functional theory (DFT), molecular dynamics simulations (MD), normal mode analysis (NMA), and SwissADME profiling. Compounds 2g, 2d, and 2b emerged as potent inhibitors with IC50 values of 5.48 ± 0.18 to 9.44 ± 0.32 µM, outperforming the reference thiourea (IC50 = 22.13 ± 2.82 µM). Structure-Activity Relationship (SAR) analysis revealed that electron-withdrawing nitro substituents at para positions dramatically enhanced inhibitory potency. Docking investigation demonstrated robust interactions with the urease active site that includes binuclear nickel center and residues His492, His519, and Asp633. DFT calculations established strong correlations between chemical reactivity indices and biological activity. Molecular docking and MD simulations validated stable binding interactions with key residues (His492, His519, and Asp633). NMA revealed enhanced flap flexibility (λ1 = 1.39 × 10-6) and motional coupling upon 2g binding.
Conclusion: These results expose the synthesized compounds, especially 2g as a potent urease inhibitor and provide a valuable insight for future anti-urease drug development.
Contributed Indexing: Keywords: DFT analysis; Thiosemicarbazones; molecular docking; structure activity relationship; thiophene-2-carboxylic acid; urease inhibition
Substance Nomenclature: EC 3.5.1.5 (Urease)
0 (Enzyme Inhibitors)
0 (Thiosemicarbazones)
0 (Thiophenes)
3FD00JX53J (2-thiophene carboxylic acid)
0 (Carboxylic Acids)
Entry Date(s): Date Created: 20260713 Date Completed: 20260805 Latest Revision: 20260805
Update Code: 20260805
DOI: 10.1080/17568919.2026.2699672
PMID: 42439821
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1756-8927
DOI:10.1080/17568919.2026.2699672