Synthesis, spectroscopic characterization, structural studies, and In Vitro antitumor activities of Pyridine-3-carbaldehyde Thiosemicarbazone derivatives

Abstract

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4 '-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3 ',4 '-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3 ',5 '-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (H-1,C-13,F-19) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of7has been also confirmed by single crystal X-ray diffraction. In the solid state7exists in theEconformation about the N2-N3 bond;7also presents theEconformation in solution, as evidenced by(1)H NMR spectroscopy. Thein vitroantitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC(50)and the selectivity index (SI) was calculated. Biological studies revealed that1(IC50 = 3.36 to 21.35 mu M) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 mu M) against different types of human tumor cell lines.1was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by1towards the HuTu80 and MCF7 tumor cell lines, as compared to that of5-FU. Therefore,1can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the5-FUanticancer drug against the 3T3 mouse embryo fibroblast cells.