Altuğ-Tasa Burcugül, Kaya-Çavuşoğlu Betül, Koparal Ayşe T, Turan Gülhan, Koparal Ali S, Kaplancıklı Zafer A
Department of Biology, Faculty of Science, Eskisehir Technical University, Eskisehir, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Bulent Ecevit University, 67100 Zonguldak, Turkey.
Anticancer Agents Med Chem. 2021;21(15):2041-2049. doi: 10.2174/1871520621666201231143535.
Thiadiazole has attracted a great deal of interest as a versatile heterocycle for the discovery and development of potent anticancer agents. Thiadiazole derivatives exert potent antitumor activity against a variety of human cancer cell lines through various mechanisms.
The goal of this work was to design and synthesize thiadiazole-based anticancer agents with anti-angiogenic activity.
N-aryl-2-[(5-(aryl)amino-1,3,4-thiadiazol-2-yl)thio]acetamides (4a-r) were synthesized via the reaction of 5-(aryl)amino-1,3,4-thiadiazole-2(3H)-thiones with N-(aryl)-2-chloroacetamides in the presence of potassium carbonate. The compounds were investigated for their cytotoxic effects on three cancer (A549, HepG2, SH-SY5Y), two normal (HUVEC and 3T3-L1) cell lines using MTT and WST-1 assays. In order to examine whether the compounds have anti-angiogenic effects or not, HUVECs were cultured on matrigel matrix to create a vascular-like tube formation.
Compounds 4d, 4m and 4n were more effective on A549 human lung adenocarcinoma cells than cisplatin. The IC values of compounds 4d, 4m and 4n for A549 cell line were found to be 7.82 ± 0.4, 12.5 ± 0.22, 10.1 ± 0.52 μM, respectively when compared with cisplatin (IC= 20 ± 0.51 μM), whilst their IC values for HUVEC cell line were determined as 138.7 ± 0.84, 78 ± 0.44, 177.6 ± 0.2 μM, respectively after 48 h of the treatment. The concentrations (10-20-50 μM) of compounds 4d, 4e, 4l, 4m, 4n, 4q and 4r were found to inhibit vascular like tube formation.
According to their anticancer and anti-angiogenic effects, compounds 4d, 4m and 4n may be potential anticancer agents for further in vivo studies.
噻二唑作为一种通用的杂环化合物，在强效抗癌药物的发现和开发方面引起了广泛关注。噻二唑衍生物通过多种机制对多种人类癌细胞系发挥强效抗肿瘤活性。
本研究旨在设计并合成具有抗血管生成活性的基于噻二唑的抗癌药物。
通过5-（芳基）氨基-1,3,4-噻二唑-2（3H）-硫酮与N-（芳基）-2-氯乙酰胺在碳酸钾存在下反应合成N-芳基-2-[(5-（芳基）氨基-1,3,4-噻二唑-2-基）硫代]乙酰胺（4a-r）。使用MTT和WST-1测定法研究这些化合物对三种癌细胞（A549、HepG2、SH-SY5Y）和两种正常细胞（HUVEC和3T3-L1）系的细胞毒性作用。为了检测这些化合物是否具有抗血管生成作用，将HUVECs接种在基质胶上以形成血管样管结构。
化合物4d、4m和4n对A549人肺腺癌细胞的作用比顺铂更有效。与顺铂（IC = 20±0.51μM）相比，化合物4d、4m和4n对A549细胞系的IC值分别为7.82±0.4、12.5±0.22、10.1±0.52μM，而在处理48小时后，它们对HUVEC细胞系的IC值分别测定为138.7±0.84、78±0.44、177.6±0.2μM。发现化合物4d、4e、4l、4m、4n、4q和4r的浓度（10-20-50μM）可抑制血管样管形成。
根据其抗癌和抗血管生成作用，化合物4d、4m和4n可能是进一步体内研究的潜在抗癌药物。
