Design, synthesis and in vitro evaluation of new thiosemicarbazone derivatives as potential anticancer agents

Abstract

Thiosemicarbazones play a pivotal role as potential therapeutic agents for the management of lung cancer. 4-(4-Cyanophenyl)-1-[(5-arylfuran-2-yl)methylene]thiosemicarbazides (1-10) were obtained via the reaction of 4-(4-cyanophenyl)thiosemicarbazide with 5-arylfurfurals. MTT assay was performed to assess their cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse fibroblast cell lines. Compounds 1, 5, 6 and 7 were identified as the most effective anticancer agents on A549 cell line with IC50 values of 12.75 +/- 0.35 mu g/mL, 4.30 +/- 0.61 mu g/mL, 5.50 +/- 2.12 mu g/mL and 5.90 +/- 0.57 mu g/mL, respectively compared to cisplatin (IC50 = 12.00 +/- 0.71 mu g/mL). The IC50 values of these compounds for L929 cell line were higher than their IC50 values for A549 cell line indicating that their anticancer effects were selective. The apoptotic effects of these compounds were also analyzed based on Annexin V-PI binding capacities in flow cytometry. According to flow cytometric analyses, the early apoptotic effects of compounds 1, 5, 6 and 7 on A549 cell line were determined as 4.7, 5.1, 7.3 and 5.1%, whereas their late apoptotic effects were determined as 3.7, 2.0, 4.9 and 3.3%, respectively. Compound 6 showed more apoptotic activity than compounds 1, 5 and 7. According to these findings, compounds 5 and 6 stand out as promising anticancer agents for further in vitro and in vivo studies.