Synthesis and biological evaluation of a novel photo-activated histone deacetylase inhibitor
作者:Gopal R. Sama、Hongbin Liu、Simon Mountford、Phillip Thompson、Andrea Robinson、Anthony E. Dear
DOI:10.1016/j.bmcl.2020.127291
日期:2020.8
Hydroxamic acid-based histone deacetylase inhibitors (HDACi) are a class of epigenetic agents with potentially broad therapeutic application to several disease states including post angioplasty mediated neo-intimal hyperplasia (NIH). Precise spatiotemporal control over the release of HDACi at the target blood vessel site is required for the safe and successful therapeutic use of HDACi in the setting
基于异羟肟酸的组蛋白脱乙酰基酶抑制剂(HDACi)是一类表观遗传药物,对包括血管成形术后介导的新内膜增生(NIH)在内的几种疾病都有潜在的广泛治疗应用。为了在NIH药物洗脱球囊导管(DEBc)血管成形术治疗中安全且成功地使用HDACi,需要对目标血管部位HDACi的释放进行精确的时空控制。我们旨在开发和表征新型光敏性HDACi(metacept-3 1),作为DEBc的潜在涂层剂。 Metacept-3 1被笼罩着对光不稳定的保护基(PPG),以合成新型UV365nm活性HDACi,笼养的metacept-3 15。笼metacept-3的转化率15到有源/天然metacept-3 1通过UV365nm在显著数量和在毫瓦(MW)范围UV365nm功率电平实现的。 对笼中的metacept-3 15进行UV365nm活化前后的生物学活性的体外评估发现,暴露于短时间,mW范围的UV365nm的