Synthesis, SARS-CoV-2 3CL main protease inhibitor, anti-inflammatory, and wound-healing effects of a zinc(II)-thiosemicarbazone complex

A new zinc(II) complex with tetradentate thiosemicarbazone (2) was synthesized to investigate the effectiveness against SARS-CoV-2 virus and its anti-inflammatory effects on BEAS-2B human bronchial epithelial cells. Structural confirmation was performed by IR, H-1 and C-13 NMR, and ESI-MS spectroscopies. The results showed that the complex 2 molecule inhibits 3CL main protease enzyme. It was found that complex 2 had a proliferative effect at low doses. TNF-alpha stimulation significantly increased IL8 gene expression 3.42 +/- 0.107 fold in BEAS-2B cells (p = 0.037). However, it was found that all concentrations of complex 2 highly suppressed IL8 gene expression in the control group and TNF-alpha-stimulated BEAS-2B cells (p = 0.009). The healing rate of complex 2 was higher than the control and BEAS-2B cells induced by TNF-alpha at the 24 and 48 h after wound formation. It is known that the biological efficiency of metal-thiosemicarbazone complexes was adjusted depending on substituent and metal. In this context, complex 2 may be considered as a precursor molecule in the investigation of the antiviral and anti-inflammatory effects of those formed with the element zinc. Investigation of the selectivity of the inhibitory effect of complex 2 on the 3CL main protease is important for a more detailed understanding of its antiviral effect potential. Although the 3CL main protease enzyme was concentrated in antiviral effective molecule screening studies against SARS-CoV-2 virus, the fact that complex 2 also has anti-inflammatory and wound-healing effects is a distinguishing feature from other inhibitory effective molecules.