合成 1,2,4-三唑连接的脲/硫脲缀合物作为细胞毒性和诱导凋亡试剂。
Synthesis of 1,2,4-triazole-linked urea/thiourea conjugates as cytotoxic and apoptosis inducing agents.
机构信息
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
出版信息
Bioorg Med Chem Lett. 2018 Jun 1;28(10):1919-1924. doi: 10.1016/j.bmcl.2018.03.074. Epub 2018 Mar 28.
A new series of 1,2,4-triazole-linked urea and thiourea conjugates have been synthesized and evaluated for their in vitro cytotoxicity against selected human cancer cell lines namely, breast (MCF-7, MDA-MB-231), lung (A549) prostate (DU145) and one mouse melanoma (B16-F10) cell line and compared with reference drug. The compound 5t showed significant cytotoxicity on MCF-7 breast cancer cell line with a IC value of 7.22 ± 0.47 µM among all the tested compounds. Notably, induction of apoptosis by compound 5t on MCF-7 cells was evaluated using different staining techniques such as acridine orange/ethidium bromide (AO/EB), annexin V-FITC/PI, and DAPI. Further, clonogenic assay indicates the inhibition of colony formation on MCF-7 cells by compound 5t. Moreover, the flow-cytometric analysis also revealed that compound 5t caused the arrest of cells at G0/G1 phase of cell cycle. In addition, the compounds when tested on normal human cells (L-132) were found to be safer with low cytotoxicity profile.
已合成了一系列新的 1,2,4-三唑连接的脲和硫脲缀合物，并对其进行了体外细胞毒性评估，针对的是选定的人类癌细胞系，包括乳腺癌（MCF-7、MDA-MB-231）、肺癌（A549）、前列腺癌（DU145）和一种小鼠黑色素瘤（B16-F10）细胞系，并与参比药物进行了比较。在所有测试的化合物中，化合物 5t 对 MCF-7 乳腺癌细胞系表现出显著的细胞毒性，IC 值为 7.22±0.47µM。值得注意的是，通过不同的染色技术，如吖啶橙/溴化乙锭（AO/EB）、Annexin V-FITC/PI 和 DAPI，评估了化合物 5t 对 MCF-7 细胞的凋亡诱导作用。此外，集落形成抑制试验表明，化合物 5t 抑制 MCF-7 细胞的集落形成。此外，流式细胞术分析还表明，化合物 5t 导致细胞周期停滞在 G0/G1 期。此外，当在正常人类细胞（L-132）上进行测试时，这些化合物被发现具有较低的细胞毒性特征，安全性更高。
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