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甲硫基磺酸盐衍生物作为信号转导和转录激活因子3（STAT3）-Src同源2（SH2）结构域的配体

Methanethiosulfonate derivatives as ligands of the STAT3-SH2 domain.

作者信息

Gabriele Elena, Ricci Chiara, Meneghetti Fiorella, Ferri Nicola, Asai Akira, Sparatore Anna

机构信息

a Department of Pharmaceutical Sciences , Università degli Studi di Milano , Milano , Italy.

b Department of Pharmacological and Biomolecular Sciences , Università degli Studi di Milano , Milano , Italy.

出版信息

J Enzyme Inhib Med Chem. 2017 Dec;32(1):337-344. doi: 10.1080/14756366.2016.1252757.

DOI:10.1080/14756366.2016.1252757
PMID:28097912
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6009886/
Abstract

With the aim to discover new STAT3 direct inhibitors, potentially useful as anticancer agents, a set of methanethiosulfonate drug hybrids were synthesized. The in vitro tests showed that all the thiosulfonic compounds were able to strongly and selectively bind STAT3-SH2 domain, whereas the parent drugs were completely devoid of this ability. In addition, some of them showed a moderate antiproliferative activity on HCT-116 cancer cell line. These results suggest that methanethiosulfonate moiety can be considered a useful scaffold in the preparation of new direct STAT3 inhibitors. Interestingly, an unusual kind of organo-sulfur derivative, endowed with valuable antiproliferative activity, was occasionally isolated. [Formula: see text].

摘要

为了发现可能用作抗癌剂的新型STAT3直接抑制剂，合成了一组甲硫基磺酸盐药物杂化物。体外试验表明，所有硫代磺酸化合物都能强烈且选择性地结合STAT3-SH2结构域，而母体药物则完全没有这种能力。此外，其中一些化合物对HCT-116癌细胞系表现出适度的抗增殖活性。这些结果表明，甲硫基磺酸盐部分可被视为制备新型直接STAT3抑制剂的有用支架。有趣的是，偶尔会分离出一种具有有价值抗增殖活性的不寻常有机硫衍生物。[分子式：见原文]

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/5a458b44f948/IENZ_A_1252757_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/d25d05b4f34c/IENZ_A_1252757_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/e7f29c133fb5/IENZ_A_1252757_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/205689ccb222/IENZ_A_1252757_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/1d40879b7538/IENZ_A_1252757_SCH0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/79a740200926/IENZ_A_1252757_SCH0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/5a458b44f948/IENZ_A_1252757_F0003_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/d25d05b4f34c/IENZ_A_1252757_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/e7f29c133fb5/IENZ_A_1252757_F0002_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/205689ccb222/IENZ_A_1252757_SCH0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/1d40879b7538/IENZ_A_1252757_SCH0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/79a740200926/IENZ_A_1252757_SCH0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc6/6009886/5a458b44f948/IENZ_A_1252757_F0003_C.jpg

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