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-(4cyanophenyl)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 µg/mL, 4.30±0.61 µg/mL, 5.50±2.12 µg/mL and 5.90±0.57 µg/mL, respectively compared to cisplatin (IC50= 12.00±0.71 µg/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.

Design, synthesis and biological evaluation of new bis(thiosemicarbazone) derivatives as potential targeted anticancer agents for non-small cell lung cancer

“…A mixture of p-phenylene diisothiocyanate (0.1 mol) and hydrazine hydrate (0.2 mol) in ethanol (30 mL) was stirred at room temperature for 4 h. Upon completion of the reaction, the precipitate was collected by filtration. The product was crystallized from ethanol [20]. (1,4-phenylene)bis (2-((5-arylfuran-2-yl)methylene)hydrazine-1-carbothioamide) derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) A mixture of 1,4-phenylenebis(thiosemicarbazide) (0.01 mol) and 5-arylfurfural (0.01 mol) was refluxed in ethanol for 8 h. Upon completion of the reaction, the mixture was cooled and the precipitate was collected by filtration.…”

“…(1,4-phenylene)bis (2-((5-arylfuran-2-yl)methylene)hydrazine-1-carbothioamide) derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11) A mixture of 1,4-phenylenebis(thiosemicarbazide) (0.01 mol) and 5-arylfurfural (0.01 mol) was refluxed in ethanol for 8 h. Upon completion of the reaction, the mixture was cooled and the precipitate was collected by filtration. The product was crystallized from ethanol [20]. (1,4-phenylene)bis (2-((5-(4-chlorophenyl)furan-2-yl)methylene)hydrazine-1-carbothioamide) (1) M.p.…”

“…A549 Human lung adenocarcinoma (ATCC ® CCL-185 ™ ) and L929 mouse fibroblast (ATCC ® CRL-6364™) cell lines were cultured and drug treatments were carried out as previously described [20].…”

“…The strong metal-chelating/metal-interacting properties of TSCs have led to the development of potent anticancer drugs due to the fact that tumor cells require essential metals for growth and proliferation. TSCs have an impressive ability to suppress the growth and proliferation of a variety of tumors through the promotion of apoptosis, cell cycle arrest and inhibition of molecular targets involved in the pathogenesis of cancer [11][12][13][14][15][16][17][18][19][20][21][22]. Over the past decade, TSCs have also been reported to show pronounced inhibitory effects on COX enzymes [23,24].…”

“…Taking into account the knowledge obtained so far [18][19][20] and the potential of TSCs for the treatment of cancer [11][12][13][14][15][16][17][18][19][20], herein we reported the preparation of new bis(thiosemicarbazone) derivatives and in vitro studies related to their cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse fibroblast (normal) cells. In order to provide a mechanistic insight into their mode of action, the potent and selective anticancer agents in this series were investigated for their effects on apoptosis, mitochondrial membrane potential and COXs.…”