化学
HDAC6型
乙酰化
异羟肟酸
HDAC1型
药理学
表观遗传学
选择性
药品
效力
组蛋白
立体化学
组蛋白脱乙酰基酶
癌症研究
生物化学
体外
基因
医学
催化作用
生物
作者
Kapil Kumar,Ranjana Das,Barsha Thapa,Bharti Rakhecha,Sapna Srivastava,Kumari Savita,Monazza Israr,Debabrata Chanda,Dibyendu Banerjee,Karuna Shanker,DU Bawankule,Benedetta Santini,Maria Luisa Di Paolo,Lisa Dalla Via,Daniele Passarella,Arvind S. Negi
标识
DOI:10.1016/j.bmc.2023.117300
摘要
Abnormal epigenetics has been recognised as an early event in tumour progression and aberrant acetylation of lysine in particular has been understood in tumorigenesis. Therefore, it has become an attractive target for anticancer drug development. However, HDAC inhibitors have limited success due to toxicity and drug resistance concerns. Present study deals with design and synthesis of bivalent indanone based HDAC6 and antitubulin ligands as anticancer agents. Two of the analogues 9 and 21 exhibited potent antiproliferative activities (IC50, 0.36–3.27 µM) and high potency against HDAC 6 enzyme. Compound 21 showed high selectivity against HDAC 6 while 9 exhibited low selectivity. Both the compounds also showed microtubule stabilization effects and moderate anti-inflammatory effect. Dual targeted anticancer agents with concomitant anti-inflammatory effects will be more attractive clinical candidates in future.
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