Initially, the selective COX-2 inhibitors were developed as safer alternatives to the conventional NSAIDs, but later on, most of them were withdrawn from the market due to the risk of heart attack and stroke. Celecoxib, the first selective COX-2 inhibitor, was approved by the Food and Drug Administration (FDA) in December 1998 and was taken back from the market in 2004. Since then, many coxibs have been discontinued one by one due to adverse cardiovascular events. United States (US), Australian and European authorities related to Therapeutic Goods Administration (TGA) implemented the requirements to carry the "Black box" warning on the labels of COX-2 drugs highlighting the risks of serious cardiovascular events. These facts encouraged the researchers to explore them well and find out the biochemical basis behind the cardiotoxicity. From the last few decades, the molecular mechanisms behind the coxibs have regained the attention, especially the specific structural features of the selective COX-2 inhibitors that are associated with cardiotoxicity. This review discusses the key structural features of the selective COX-2 inhibitors and underlying mechanisms that are responsible for the cardiotoxicity. This report also unfolds different strategies that have been reported in the last 10 years to combat the problem of selective COX-2 inhibitors mediated cardiotoxicity.

中文翻译：

---

选择性COX-2抑制剂介导的心脏毒性的结构研究：综述。

最初，选择性COX-2抑制剂被开发为常规NSAID的更安全替代品，但后来，由于心脏病和中风的风险，大多数抑制剂被撤出市场。Celecoxib是第一种选择性COX-2抑制剂，于1998年12月获得美国食品药品监督管理局（FDA）的批准，并于2004年从市场上撤回。此后，由于心血管不良事件，许多Coxib逐渐被停用。 。美国（澳大利亚），澳大利亚和欧洲与药品管理局（TGA）有关的当局实施了要求，要求在COX-2药物标签上带有“黑匣子”警告，强调严重心血管事件的风险。这些事实鼓励研究人员深入研究它们，并找出心脏毒性背后的生化基础。在最近的几十年中，coxib的分子机制重新引起了人们的关注，特别是与心脏毒性有关的选择性COX-2抑制剂的特定结构特征。这篇综述讨论了选择性COX-2抑制剂的关键结构特征以及引起心脏毒性的潜在机制。该报告还提出了最近十年来针对对抗选择性COX-2抑制剂介导的心脏毒性问题的不同策略。这篇综述讨论了选择性COX-2抑制剂的关键结构特征以及引起心脏毒性的潜在机制。该报告还提出了最近十年来针对对抗选择性COX-2抑制剂介导的心脏毒性问题的不同策略。这篇综述讨论了选择性COX-2抑制剂的关键结构特征以及引起心脏毒性的潜在机制。该报告还提出了最近十年来针对对抗选择性COX-2抑制剂介导的心脏毒性问题的不同策略。