Synthesis, kinetics and biological assay of some novel aryl bis-thioureas: A potential drug candidates for Alzheimer's disease

Rabail Ujan, Pervaiz Ali Channar, Ali Bahadur, Qamar Abbas, Mazloom Shah, S. G. Rashid, Shahid Iqbal, Aamer Saeed, Hisham S.M. Abd-Rabboh, Hussain Raza, Mubashir Hassan, Ali Nawaz Siyal, Parvez Ali Mahesar, Bhajan Lal, Kashif Ali Channar, Bilal Ahmad Khan, Muhammad Nawaz, Muhammad Shahid Riaz Rajoka, Jung Min Kim

Research output: Journal PublicationArticlepeer-review

8 Citations (Scopus)


A new series of bis-thioureas (4a-4j) was synthesized and characterized through spectroscopic and elemental analysis. The synthesized compounds 4a-4j were subjected to acetylcholinesterase enzyme (AChE) inhibition activity and free radical scavenging activity. The results of AChE inhibition assay were found to be active in inhibiting the target enzyme with different IC50 values. Among all derivatives, the 4 g showed highly potent inhibition potential against AChE enzyme with IC50 value of 0.1761±0.00768 µM, which is several times better than the reference inhibitor neostigmine methylsulfate IC50 2.469±0.069 µM. The initial structure-activity relationship (SAR) of 4 g revealed dual hydrogen bonding ability (donor and acceptor). Moreover, the electronic environment around the aromatic ring also greatly influenced the enzyme inhibition of AChE. To further explore the newly synthesized AChE inhibitors, kinetic studies were carried out to determine the mode of inhibition and it was found to be competitive inhibition. Pharmacokinetic predictions (ADMET parameters) were also evaluated and compounds showed good lead-like potential with little hepatotoxic and no skin-sensitive effects. The molecular docking studies delineated the binding affinity of the ligands with target protein and showed docking scores in the range of -10.3 to -7.6 kcal/mol.

Original languageEnglish
Article number131136
JournalJournal of Molecular Structure
Publication statusPublished - 15 Dec 2021
Externally publishedYes


  • AChE inhibitors
  • Antioxidant
  • Bis-thiourea
  • Kinetic Mechanism
  • Molecular docking
  • Pharmacokinetics ADMET parameters

ASJC Scopus subject areas

  • Analytical Chemistry
  • Spectroscopy
  • Organic Chemistry
  • Inorganic Chemistry


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