The latest advances in the discovery of nitric oxide hybrid drug compounds.

INTRODUCTION: 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.