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. 2021 Sep 8;22(18):9709.
doi: 10.3390/ijms22189709.

Novel Coumarin-Thiadiazole Hybrids and Their Cu(II) and Zn(II) Complexes as Potential Antimicrobial Agents and Acetylcholinesterase Inhibitors

Dariusz Karcz  1 , Karolina Starzak  1 , Ewa Ciszkowicz  2 , Katarzyna Lecka-Szlachta  2 , Daniel Kamiński  3 , Bernadette Creaven  4 , Hollie Jenkins  5 , Piotr Radomski  1 , Anna Miłoś  6 , Lidia Ślusarczyk  7 , Arkadiusz Matwijczuk  7
Affiliations

Novel Coumarin-Thiadiazole Hybrids and Their Cu(II) and Zn(II) Complexes as Potential Antimicrobial Agents and Acetylcholinesterase Inhibitors

Dariusz Karcz et al. Int J Mol Sci. .

Abstract

A series of coumarin-thiadiazole hybrids and their corresponding Cu(II) and Zn(II) complexes were synthesized and characterized with the use of spectroscopic techniques. The results obtained indicate that all the coumarin-thiadiazole hybrids act as bidentate chelators of Cu(II) and Zn(II) ions. The complexes isolated differ in their ligand:metal ratio depending on the central metal. In most cases, the Zn(II) complexes are characteristic of a 1:1 ligand:metal ratio, while in the Cu(II) complexes the ligand:metal ratio is 2:1. All compounds were tested as potential antibacterial agents against Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacterial strains demonstrating activities notably lower than commercially available antibiotics. The more promising results were obtained from the assessment of antineurodegenerative potency as all compounds showed moderate acetylcholinesterase (AChE) inhibition activity.

Keywords: acetylcholinesterase inhibitors; antibacterial activity; antimicrobial; complexes; coumarin; hybrids; neurodegeneration; thiadiazole.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Synthetic pathway for the synthesis of coumarin-thiadiazole hybrids (2–5) and their corresponding Cu(II) and Zn(II) complexes 6–13: (A) H2SO4, 25 °C; (B) POCl3, thiosemicarbazide, 75 °C; (C) Cu(CH3COO)2xH2O, EtOH/H2O, reflux; (D) Zn(CH3COO)2xH2O, EtOH/H2O, reflux. For clarity, the aqua ligands in the complexes were omitted from the above figure.
Figure 2
Figure 2
Structures of coumarin-thiadiazole hybrids and their corresponding Zn(II) complexes showing the numbering system of atoms.
Figure 3
Figure 3
Comparison of IR (ATR) spectra of the coumarin-thiadiazole hybrids 2–5.
Figure 4
Figure 4
Proposed enol (left) and keto (right) tautomeric forms of the coumarin-thiadiazole hybrids 2–5.
Figure 5
Figure 5
Comparison of IR (ATR) spectra of the coumarin-thiadiazole hybrid 3 and its corresponding Cu(II) and Zn(II) complexes (7 and 11, respectively).
Figure 6
Figure 6
1H-NMR spectra of coumarin-thiadiazole hybrids (2–5) in DMSO-d6 (water and residual DMSO signals [42] are removed for better clarity).
Figure 7
Figure 7
1H-NMR (DMSO-d6) spectrum of Zn(II) complex 10 with expansions showing signals originating from the aqueous and acetate ligands.
Figure 8
Figure 8
Crystal structure of the Zn(II) complex 11: Asymmetric part of the crystal structure (A), simplified 2D image of the complex (B), coordination spheres around Zn(II) ions in the complex (C). The thermal displacement ellipsoids are with 50% of probability.
Figure 9
Figure 9
Electronic absorption spectra of 0.2 mM solutions (A) and fluorescence emission spectra 0.1 mM solutions (B) of coumarin-thiadiazole hybrids 2–5 and their corresponding Cu(II) and Zn(II) complexes 6–13.
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