The free radical nitric oxide (NO) is considered one of the most versatile endogenous molecules
and is a crucial signalling molecule in numerous biochemistry pathways of the human body. NO
is directly related to pathological processes and plays an important role in many different and interrelated
physiological processes. In some cases, a depletion of NO or an attenuation of its effector system
could exist as in hypertension, angina and impotence; in others, an overproduction of NO may be a
major cause of damage, as in circulatory shock, sepsis, neurodegenerative disorders and inflammatory
responses. By using certain functional groups present in molecules that already have potential therapeutic
value, hybrid compounds, by means of inclusion of NO-donors (e.g., ester nitrates and nitrites,
S-nitrosothiols, metal complexes, furoxans, oxadiazoles, diazeniumdiolates and NO nanoparticles), can
be developed that have a NO release benefit along with maintaining the activity of the native drug. The
objective of the design of NO-donor hybrid compounds is to achieve a balance between the release of
therapeutic amounts of NO, especially in the site of action, and maintaining the native drug activity.
This review explores some of the most promising recent advances in NO-donor drug development and
addresses the challenges associated with NO as a therapeutic agent.