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

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

Faizan Ur Rahman  1 , Maryam Bibi  2 , Ezzat Khan  1   2 , Abdul Bari Shah  3 , Mian Muhammad  1 , Muhammad Nawaz Tahir  4 , Adnan Shahzad  5 , Farhat Ullah  6 , Muhammad Zahoor  7 , Salman Alamery  8 , Gaber El-Saber Batiha  9
Affiliations

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

Faizan Ur Rahman et al. Molecules. .

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.

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Conflict of interest statement

The authors have no potential conflict of interest to declare.

Figures

Figure 1
Figure 1
Structure of unsymmetrical thiourea derivatives, 1-cyclohexyl-3-(iso-butyl)thiourea (1), 1-cyclohexyl-3-(tert-butyl)thiourea (2), 1-cyclohexyl-3-(3-chlorophenyl)thiourea (3), 1-phenyl-3-(1,1-dibutyl)thiourea (4), 1-phenyl-3-(2-chlorophenyl)thiourea (5) and 1-phenyl-3-(4-chlorophenyl)thiourea (6) used in this study.
Figure 2
Figure 2
X-ray structure of Compound 3 (left), ellipsoids are drawn at 50% probability level, H atoms are omitted, selected carbon atoms and all non-carbon atoms are numbered. Dimer of compound 3 (right) stabilized through N1H–S1 interactions. Other secondary interactions in molecules were not detected. For data related to structural determination and refinements and selected structural parameters (bond lengths and angles) see Table 1 and Table 2, respectively.
Figure 3
Figure 3
Single crystal structure (left hand) of compound 4, ellipsoids are drawn at 50% probability level, H-atoms except NH and CH2 are omitted and selected atoms have been numbered. A cyclic hexamer (right hand) is shown, molecules are linked with the help of S–H interactions making a macrocyclic ring containing six thiourea molecules (See Table 2 for selected structural parameters).
Figure 4
Figure 4
Different view of supramolecular structure of compound 4, single layer of mutually connected hexameric units (top), mutually connected layers (middle and bottom), the molecular architecture extends in a 3D manner.
Figure 5
Figure 5
Optimized structures of compounds 3 and 4, selected hydrogen atoms are omitted.
Figure 6
Figure 6
3D binding interaction modes of compounds 3 and 4 as inhibitor of AChE and BChE. (a) Interaction posing of compound 3 with AChE; (b) interaction of compound 4 with AChE; (c) interaction of compound 3 with BChE and (d) interaction of compound 4 with BChE.
Figure 7
Figure 7
Fluorescence spectra of 3 and 5 as two representative examples.
Figure 8
Figure 8
Representative fluorescence spectra of 3 and 5 as a function of concentration of Hg(II) ion.
See this image and copyright information in PMC

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