发现 5-磺酰基四唑类化合物作为神经母细胞瘤分化剂。
Discovery of 5-sulfonyltetrazoles as neuroblastoma differentiation agents.
机构信息
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
Department of Chemistry and Biochemistry, Texas State University, San Marcos, TX 78666, USA.
出版信息
Bioorg Med Chem Lett. 2023 Oct 1;94:129455. doi: 10.1016/j.bmcl.2023.129455. Epub 2023 Aug 18.
Previously, we developed an innovative high-content screening (HCS) approach to quantify neuroblastoma cell differentiation based on neurite outgrowth, a morphological differentiation marker of neuroblastoma cells. Here, we report the utilization of this platform to identify 1-methyl-5-(ethylsulfonyl)-1H-tetrazole (3a) as a new neuroblastoma differentiation agent using the ChemBridge Diverset commercial synthetic small molecule compound library. We show that this activity can be extended to a group of analogues, which can be accessed via a short two-step synthetic sequence. A new analogue, 5-(allylsulfonyl)-1-methyl-1H-tetrazole (3c) was identified in this synthetic effort as a compound that has even more pronounced differentiation and cytotoxic activities than the original hit compound 3a.
此前，我们开发了一种创新的高通量筛选（HCS）方法，基于神经突生长来量化神经母细胞瘤细胞的分化，这是神经母细胞瘤细胞的形态分化标志物。在这里，我们报告了利用该平台，使用 ChemBridge Diverset 商业合成小分子化合物库，将 1-甲基-5-（乙基磺酰基）-1H-四唑（3a）鉴定为一种新的神经母细胞瘤分化剂。我们表明，这种活性可以扩展到一组类似物，这些类似物可以通过短的两步合成序列获得。在这项合成工作中，我们发现了一种新的类似物，5-（烯丙基磺酰基）-1-甲基-1H-四唑（3c），它比原始命中化合物 3a 具有更明显的分化和细胞毒性活性。
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