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 (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor 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 IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 μM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 μM) against different types of human tumor cell lines. 1 was 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 by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can 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 the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells.

中文翻译：

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Pyridine-3-carbaldehyde Thiosemiccarbazone 衍生物的合成、光谱表征、结构研究和体外抗肿瘤活性

八种新型缩氨基硫腙衍生物，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),来自相应的吡啶-3-甲醛与氨基硫脲的反应。合成的化合物通过 ESI-Mass、UV-Vis、IR 和 NMR（1H、13C、19F）光谱技术进行表征。摩尔质量值和光谱数据与提出的结构式一致。7的分子结构也已通过单晶X射线衍射证实。在固态时，7 以 E 构象围绕 N2-N3 键存在；图7还呈现了溶液中的E构象，如1H NMR光谱所证明的。在六种人类肿瘤细胞系上研究了合成化合物的体外抗肿瘤活性：H460（肺大细​​胞癌）、HuTu80（十二指肠腺癌）、DU145（前列腺癌）、MCF-7（乳腺癌）、M-14（黑色素瘤）和 HT-29（结肠腺癌）。此外，对制备的化合物在 3T3 正常细胞中进行了毒性研究。结果表示为IC50并计算选择性指数(SI)。生物学研究表明 1 (IC50 = 3. 与其他测试的缩氨基硫脲（IC50 = 40.00 至 > 582.26 μM）相比，36 至 21.35 μM）对不同类型的人类肿瘤细胞系显示出最高的抗增殖活性。发现 1 对 M14 细胞系的细胞毒性 (SI = 1.82) 是 5-氟尿嘧啶 (5-FU) 的两倍，表明其即使在低浓度下也能有效抑制细胞生长。与 5-FU 相比，1 对 HuTu80 和 MCF7 肿瘤细胞系的活性略低。因此，1 可以被认为是用作药理剂的有希望的候选物，因为它具有显着的活性，并且被发现比 5-FU 抗癌药物对 3T3 小鼠胚胎成纤维细胞更无害。与其他测试的缩氨基硫脲 (IC50 = 40.00 至 >582.26 μM) 相比，它针对不同类型的人类肿瘤细胞系。发现 1 对 M14 细胞系的细胞毒性 (SI = 1.82) 是 5-氟尿嘧啶 (5-FU) 的两倍，表明其即使在低浓度下也能有效抑制细胞生长。与 5-FU 相比，1 对 HuTu80 和 MCF7 肿瘤细胞系的活性略低。因此，1 可以被认为是用作药理剂的有希望的候选物，因为它具有显着的活性，并且被发现比 5-FU 抗癌药物对 3T3 小鼠胚胎成纤维细胞更无害。与其他测试的缩氨基硫脲 (IC50 = 40.00 至 >582.26 μM) 相比，它针对不同类型的人类肿瘤细胞系。发现 1 对 M14 细胞系的细胞毒性 (SI = 1.82) 是 5-氟尿嘧啶 (5-FU) 的两倍，表明其即使在低浓度下也能有效抑制细胞生长。与 5-FU 相比，1 对 HuTu80 和 MCF7 肿瘤细胞系的活性略低。因此，1 可以被认为是用作药理剂的有希望的候选物，因为它具有显着的活性，并且被发现比 5-FU 抗癌药物对 3T3 小鼠胚胎成纤维细胞更无害。82) 而不是 5-氟尿嘧啶 (5-FU) 对抗 M14 细胞系，表明其即使在低浓度下也能有效抑制细胞生长。与 5-FU 相比，1 对 HuTu80 和 MCF7 肿瘤细胞系的活性略低。因此，1 可以被认为是用作药理剂的有希望的候选物，因为它具有显着的活性，并且被发现比 5-FU 抗癌药物对 3T3 小鼠胚胎成纤维细胞更无害。82) 而不是 5-氟尿嘧啶 (5-FU) 对抗 M14 细胞系，表明其即使在低浓度下也能有效抑制细胞生长。与 5-FU 相比，1 对 HuTu80 和 MCF7 肿瘤细胞系的活性略低。因此，1 可以被认为是用作药理剂的有希望的候选物，因为它具有显着的活性，并且被发现比 5-FU 抗癌药物对 3T3 小鼠胚胎成纤维细胞更无害。