University of Granada researchers have tested melatonin analogues in rats as it inhibits the enzyme nitric oxide synthase (NOS), which is involved in the development of conditions as inflammatory bowel disease, septic shock or rheumatoid arthritis, as well as in neurodegenerative conditions as Huntington's disease, Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis.
Some of the new analogues developed by the University of Granada have been tested in vivo in rats and present "very interesting pharmacological properties, as they are much more efficient than melatonin" in inhibiting NOS activity in Parkinson models. Most of the results obtained in this study have been published in Journal of Medicinal Chemistry.
Melatonin is a hormone secreted by the pineal gland that inhibits the central nervous system in rats and humans. Therefore, it is said to have neuroprotective and anticonvulsant properties. These properties give melatonin the ability to inhibit nitric oxide production, as NO is involved in numerous physiological and pathological processes. Therefore, it is necessary to regulate NO production. At present, researchers are trying to "develop powerful and selective inhibitors of each NOS isoform, which would allow clinicians to control specific pathologies, and would help determine the role of the different isoforms in the biological system".
New Inhibitors
The University of Granada researchers that participated in this study work at the Department of Pharmaceutical and Organic Chemistry and the Institute of Biotechnology of the University of Granada. Taking melatonin as a model, the researchers designed and synthesized several families of complexes (kynurenines, kynurenamines and phenyl pyrazolines), which act as NOS inhibitors. The comparative analysis of the structures of these three families of complexes "allows us to determine structure-activity relationships to inhibit the enzyme NOS and develop a model that might be used to design new inhibitors of this enzyme", the researchers state.