TY - JOUR
T1 - Targeting xanthine oxidase by natural products as a therapeutic approach for mental disorders
AU - Martorell, Miquel
AU - Lucas, Xavier
AU - Alarcón-Zapata, Pedro
AU - Capó, Xavier
AU - Quetglas-Llabrés, Maria Magdalena
AU - Tejada, Silvia
AU - Sureda, Antoni
N1 - Publisher Copyright:
© 2021 Bentham Science Publishers.
PY - 2021
Y1 - 2021
N2 - Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines-hypoxanthine and xanthine-to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct associa-tion between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.
AB - Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines-hypoxanthine and xanthine-to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct associa-tion between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.
KW - Allopurinol
KW - Enzyme inhibition
KW - Free radicals
KW - Inflammation
KW - Natural products
KW - Xanthine oxidase
UR - http://www.scopus.com/inward/record.url?scp=85101486786&partnerID=8YFLogxK
U2 - 10.2174/1381612826666200621165839
DO - 10.2174/1381612826666200621165839
M3 - Review article
C2 - 32564744
AN - SCOPUS:85101486786
SN - 1381-6128
VL - 27
SP - 367
EP - 382
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 3
ER -