The author of 《Discovery of 1,2,4-oxadiazole-Containing hydroxamic acid derivatives as histone deacetylase inhibitors potential application in cancer therapy》 were Yang, Zhuang; Shen, Mingsheng; Tang, Minghai; Zhang, Wanhua; Cui, Xue; Zhang, Zihao; Pei, Heying; Li, Yong; Hu, Mengshi; Bai, Peng; Chen, Lijuan. And the article was published in European Journal of Medicinal Chemistry in 2019. Category: nitriles-buliding-blocks The author mentioned the following in the article:
In this study, a series of novel HDAC inhibitors containing 1,2,4-oxadiazole as the cap group, were synthesized and evaluated in vitro. Compound I, displayed the most potent histone deacetylase (HDAC) inhibition, especially against HDAC1, 2, and 3 with IC50 values of 1.8, 3.6 and 3.0 nM, resp. In vitro antiproliferative studies confirmed that I was more potent than SAHA, with IC50 values against 12 types of cancer cell lines ranging from 9.8 to 44.9 nM. The results of Western blot assays showed that compound I can significantly up-regulate the acetylation of the biomarker his-H3 and mol. docking analyses revealed the mode of action of compound I against HDAC1. The results of flow-cytometry anal. suggested that the above compound induces cell cycle arrest at the G1 phase and has apoptotic effects and further investigation of the activity on the primary cells of three patients, showed IC50 values of 21.3, 61.1, and 77.4 nM. More importantly, an oral bioavailability of up to 53.52% was observed for compound I. An in vivo pharmacodynamic evaluation demonstrated that compound I can significantly inhibit tumor growth in a Daudi Burkitt’s lymphoma xenograft model, with tumor inhibition rates of 53.8 and 46.1% observed at 20 and 10 mg/kg when administered p.o. and i.v., resp. These results indicate that compound I may be a suitable lead for further evaluation and development as an HDAC inhibitors and potent anticancer agents. The experimental process involved the reaction of 4-Cyanobenzyl bromide(cas: 17201-43-3Category: nitriles-buliding-blocks)
4-Cyanobenzyl bromide(cas: 17201-43-3) is an important intermediate for pharmaceutical production. It can be used for the synthesis of a series of piperidine-linked aromatic diimidazolines, which have been synthesized as conformationally restricted congeners of the anti-Pneumocystis carinii (PCP) drug, Pentamidine.Category: nitriles-buliding-blocks
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts