Thiourea Derivatives, Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors

Faizan Ur Rahman; Maryam Bibi; Ezzat Khan; Abdul Bari Shah; Mian Muhammad; Muhammad Nawaz Tahir; Adnan Shahzad; Farhat Ullah; Muhammad Zahoor; Salman Alamery; Gaber El-Saber Batiha

doi:10.3390/molecules26154506

Thiourea Derivatives, Simple in Structure but Efficient Enzyme Inhibitors and Mercury Sensors

Molecules. 2021 Jul 27;26(15):4506. doi: 10.3390/molecules26154506.

Authors

Affiliations

¹ Department of Chemistry, University of Malakand, Lower Dir 18800, Pakistan.
² Department of Chemistry, College of Science, University of Bahrain, Sakhir 32038, Bahrain.
³ Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 52828, Korea.
⁴ Department of Physics, University of Sargodha, Sargodha 40100, Pakistan.
⁵ Institute of Chemical Sciences, University of Swat, Swat 19150, Pakistan.
⁶ Department of Pharmacy, University of Malakand, Chakdara, Lower Dir 18800, Pakistan.
⁷ Department of Biochemistry, University of Malakand, Lower Dir 18800, Pakistan.
⁸ Department of Biochemistry, College of Science, King Saud University, P.O. Box 22452, Riyadh 11451, Saudi Arabia.
⁹ Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt.

Abstract

In this study six unsymmetrical thiourea derivatives, 1-isobutyl-3-cyclohexylthiourea (1), 1-tert-butyl-3-cyclohexylthiourea (2), 1-(3-chlorophenyl)-3-cyclohexylthiourea (3), 1-(1,1-dibutyl)-3-phenylthiourea (4), 1-(2-chlorophenyl)-3-phenylthiourea (5) and 1-(4-chlorophenyl)-3-phenylthiourea (6) were obtained in the laboratory under aerobic conditions. Compounds 3 and 4 are crystalline and their structure was determined for their single crystal. Compounds 3 is monoclinic system with space group P2₁/n while compound 4 is trigonal, space group R³:H. Compounds (1-6) were tested for their anti-cholinesterase activity against acetylcholinesterase and butyrylcholinesterase (hereafter abbreviated as, AChE and BChE, respectively). Potentials (all compounds) as sensing probes for determination of deadly toxic metal (mercury) using spectrofluorimetric technique were also investigated. Compound 3 exhibited better enzyme inhibition IC₅₀ values of 50, and 60 µg/mL against AChE and BChE with docking score of -10.01, and -8.04 kJ/mol, respectively. The compound also showed moderate sensitivity during fluorescence studies.

Keywords: X-ray structure; docking studies; enzyme inhibition; mercury sensing; thiourea derivatives.

MeSH terms

Acetylcholinesterase / metabolism*
Butyrylcholinesterase / metabolism*
Cholinesterase Inhibitors / chemistry
Cholinesterase Inhibitors / metabolism*
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Mercury / analysis*
Molecular Docking Simulation / methods
Molecular Structure
Protein Binding
Signal Transduction / drug effects*
Smart Materials / chemistry*
Spectrometry, Fluorescence / methods
Structure-Activity Relationship
Thiourea / analogs & derivatives*
Thiourea / chemistry
Thiourea / metabolism*
X-Ray Diffraction / methods

Substances

Cholinesterase Inhibitors
Smart Materials
Acetylcholinesterase
Butyrylcholinesterase
Mercury
Thiourea