Evaluation of Anticancer Activity of Pyruvamide 4-Allylthiosemicarbazones and Their Copper(II) Complexes Against the Leukemia THP-1 Cell Line

¹ Laboratory of Advanced Materials in Biopharmaceutics and Technics, Institute of Chemistry, Moldova State University, 60 Mateevici Street, Chisinau, MD 2009, Republic of Moldova
² Laboratory of Systematics and Molecular Phylogenetics, Institute of Zoology, Moldova State University, 1 Academiei Street, Chisinau, MD-2028, Republic of Moldova
³ Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada

Academic Editor: MARIALUIGIA FANTACUZZI

Published: 29 October 2025 by MDPI in The 1st International Electronic Conference on Medicinal Chemistry and Pharmaceutics session New Small molecules as drug candidates

Abstract:

According to recent data from the WHO and the International Agency for Research on Cancer, cancer remains one of the leading public health challenges worldwide. Projections suggest that, due to demographic factors such as population growth and aging, the annual number of new cases could reach around 35 million by 2050. The WHO report also highlights that while progress has been made in prevention and treatment, access to effective diagnostic and therapeutic options remains uneven across different regions, particularly in low- and middle-income countries. Leukemia represents a significant cause of cancer-related morbidity and mortality, and the THP-1 cell line, derived from human acute monocytic leukemia, is frequently used as an established in vitro model to evaluate the anticancer potential of new compounds. Thiosemicarbazones and their metal complexes are compounds that have long been recognized in the literature as biological agents, including those with anticancer properties.

Based on the above, for our study we synthesized a series of 4-allylthiosemicarbazones of pyruvamides: 1-(piperidin-1-yl)propane-1,2-dione 4-allylthiosemicarbazone (HL¹), 3-(morpholin-4-yl)propane-2,3-dione 4-allylthiosemicarbazone (HL²), and N-(4-methoxyphenyl)-2-oxopropanamide 4-allylthiosemicarbazone (HL³), along with their copper(II) chloride complexes [Cu(L^1-3)Cl]. The physicochemical properties of all synthesized compounds were investigated to confirm their structure and composition.

The anticancer activity of the synthesized compounds was evaluated against the THP-1 cell line. All copper(II) complexes exhibited higher activity than the corresponding thiosemicarbazones from which they were obtained. HL¹ and HL³ showed no activity, while only 3-(morpholin-4-yl)propane-2,3-dione 4-allylthiosemicarbazone demonstrated activity with an IC₅₀ value of 2.8 µM. The most active compound was [Cu(L²)Cl], with an activity value of 0.14 µM, which is 2.2 times higher than that of Doxorubicin, used as a reference standard in this study.

The work was performed with financial support from subprogram 010602 of the institutional project.

Keywords: Anticancer activity; Thiosemicarbazone; Pyruvamides; Copper(II) complexes

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