17994-94-4Relevant articles and documents
Design and synthesis of Leukotriene A4 hydrolase inhibitors to alleviate idiopathic pulmonary fibrosis and acute lung injury
Cao, Sheng,Cao, Yuting,Hou, Min,Jiang, Qiuyan,Li, Xiaohe,Lin, Gang,Liu, Xiang,Liu, Xinhua,Lu, Cheng,Mao, Jiahe,Peng, Junya,Qi, Min,Qin, Shuanglin,Song, Yang,Wei, Yujiao,Xie, Maodun,Yang, Cheng,Yang, Guang,Yang, Yuyu,Zhou, Honggang,Zhou, Yunyun
, (2020)
Idiopathic pulmonary fibrosis (IPF) and acute lung injury (ALI) are considered two severe public health issues, attributed to malfunctions of neutrophils. They can cause chronic inflammation and have association with subsequent tissue damages. There have been rare drugs applying to the efficient treatment in clinical practice. Existing research revealed that Leukotriene B4 (LTB4) is the critical endogenous molecule to induce neutrophil inflammatory response. LTB4 blocking biosynthesis is the potential strategy treating IPF and ALI. In the present study, 45 hydroxamic acid derivatives were produced, and compound 26 was screened out as a highly selective Lead compound of Leukotriene A4 Hydrolase (LTA4H), i.e., an enzyme critical to the biosynthesis of LTB4. This compound is capable of relieving neutrophilic inflammation in an IPF mouse model at early stage, as well as mitigating LPS-induced acute lung injury via a mechanism of LTB4 blocking biosynthesis in vivo. Whether this compound acts as the potential lead compound for the treatment of IPF and ALI requires further verification.
Novel antiproliferative chimeric compounds with marked histone deacetylase inhibitory activity
Giacomini, Elisa,Nebbioso, Angela,Ciotta, Alfonso,Ianni, Cristina,Falchi, Federico,Roberti, Marinella,Tolomeo, Manlio,Grimaudo, Stefania,Cristina, Antonietta Di,Pipitone, Rosaria Maria,Altucci, Lucia,Recanatini, Maurizio
, p. 973 - 978 (2014)
Given our interest in finding potential antitumor agents and in view of the multifactorial mechanistic nature of cancer, in the present work, taking advantage of the multifunctional ligands approach, new chimeric molecules were designed and synthesized by combining in single chemical entities structural features of SAHA, targeting histone deacetylases (HDACs), with substituted stilbene or terphenyl derivatives previously obtained by us and endowed with antiproliferative and pro-apoptotic activity. The new chimeric derivatives were characterized with respect to their cytotoxic activity and their effects on cell cycle progression on different tumor cell lines, as well as their HDACs inhibition. Among the other, trans-6 showed the most interesting biological profile, as it exhibited a strong pro-apoptotic activity in tumor cell lines in comparison with both of its parent compounds and a marked HDAC inhibition.
Effect of Derivatives of Hydroxamic Acids on Vasculogenic Mimicry
Balaev, A. N.,Khachatryan, D. S.,Khochenkov, D. A.,Khochenkova, Yu. A.,Kolotaev, A. V.,Machkova, Yu. S.,Ohmanovich, K. A.,Osipov, V. N.,Vartanian, A. A.
, p. 252 - 263 (2020/05/04)
Abstract—: Vasculogenic mimicry, the formation of vascular channels lined with tumor cells of a highly malignant phenotype, is currently considered as an additional system of blood supply of the tumor. Experimental studies in vivo have repeatedly demonstrated that vascular channels form in the areas of a tumor with a low density of blood vessels. It is supposed that the formation of a network of these channels inside the tumor maintains homeostasis and prevents early necrosis within it. In this work, bifunctional compounds based on a combination of quinazoline and hydroxamic acid in one molecule were examined for the ability to inhibit the migration of tumor cells and vasculogenic mimicry.
