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

Abstract

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, 1H and 13C 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‐α 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‐α‐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‐α 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.