Synthesis and Biological Evaluation of a Series of N-Substituted Pyruvamide 4-Allylthiosemicarbazones and Their Copper(II) Complexes: Antibacterial, Antiradical, and Antiproliferative Activities

A series of pyruvamide 4-allylthiosemicarbazones HL1–6 and their copper(II) chloride complexes 1–6 were synthesized. Their composition and structures were studied using elemental analysis, 1H and 13C NMR spectroscopy, and FTIR spectroscopy, as well as single-crystal X-ray diffraction analysis for thiosemicarbazones HL2, HL4, and HL6. The antiproliferative activity was evaluated against three human cancer cell lines. The copper(II) complexes exhibit higher anticancer activity than the corresponding thiosemicarbazones. Complexes 1 and 3 demonstrate the most promising anticancer properties and, in some cases, surpass the activity of doxorubicin, the reference drug. Their selectivity indices toward human leukemia THP-1 cells relative to the normal hTERT-RPE1 cell line are greater than 10. The copper(II) coordination compounds also exhibit moderate antibacterial and antifungal properties; however, this activity does not exceed that of the standard drugs. In contrast, thiosemicarbazones HL1–6 show high antiradical activity, which surpasses that of both the corresponding copper(II) complexes and Trolox. All studied biological activities strongly depend on the nature of the substituent at the nitrogen atom of the pyruvamide moiety, highlighting the potential for further exploration of substituted pyruvamides with improved activity.