Serafim Ricardo A M, Pernichelle Filipe G, Ferreira Elizabeth I
a LAPEN: Laboratory of Design and Synthesis of Chemotherapeutic Potentially Active against Neglected Diseases, Department of Pharmacy, Faculty of Pharmaceutical Sciences , University of São Paulo - FCF/USP , São Paulo , Brazil.
Expert Opin Drug Discov. 2017 Sep;12(9):941-953. doi: 10.1080/17460441.2017.1344400. Epub 2017 Jun 30.
There is a great interest in Nitric oxide (NO) within medicinal chemistry since it's involved in human signaling pathways. Prodrugs or hybrid compounds containing NO-donor scaffolds linked to an active compound are valuable, due to their potential for modulating many pathological conditions due to NO's biological properties when released in addition to the native drug. Compounds that selectively inhibit nitric oxide synthase isoforms (NOS) can also increase therapeutic capacity, particularly in the treatment of chronic diseases. However, search for bioactive compounds to efficiently and selectively modulate NO is still a challenge in drug discovery. Areas covered: In this review, the authors highlight the recent advances in the strategies used to discover NO-hybrid derivatives, especially those related to anti-inflammatory, cardiovascular, anticancer and anti-microorganism activities. They also focus on: nitric oxide synthase inhibitors, NO delivery materials and other related activities. Expert opinion: The process of molecular hybridization can be used to obtain NO-releasing compounds that also interact with different targets. The main problem with this approach is to control NO multiple actions in the right biological system. However, the use of NO-releasing groups with many different scaffolds leads to new molecular structures for bioactive compounds, suggesting synergies.
自一氧化氮（NO）参与人体信号通路以来，药物化学领域对其产生了浓厚的兴趣。含有与活性化合物相连的NO供体支架的前药或杂化化合物很有价值，因为除了天然药物外，当NO释放时，由于其生物学特性，它们具有调节多种病理状况的潜力。选择性抑制一氧化氮合酶同工型（NOS）的化合物也可以提高治疗能力，特别是在治疗慢性疾病方面。然而，在药物研发中，寻找能够有效且选择性地调节NO的生物活性化合物仍然是一项挑战。涵盖领域：在本综述中，作者强调了用于发现NO杂化衍生物所采用策略的最新进展，尤其是那些与抗炎、心血管、抗癌和抗微生物活性相关的进展。他们还关注：一氧化氮合酶抑制剂、NO递送材料及其他相关活性。专家观点：分子杂交过程可用于获得同时与不同靶点相互作用的NO释放化合物。该方法的主要问题是在正确的生物系统中控制NO的多种作用。然而，使用具有许多不同支架的NO释放基团会产生生物活性化合物的新分子结构，显示出协同作用。
