عنوان المقالة:The Design and Evaluation of a Novel Monoamine Oxidase B Inhibitor Through in Silico Approach The Design and Evaluation of a Novel Monoamine Oxidase B Inhibitor Through in Silico Approach
Hasanain Abdulhameed Odhar , Safaa Muhsen Kareem , Mohammed Ridha A Alhaideri , Mohammed Abbas Hasan , Werner J Geldenhuys
English Authors
Hasanain Abdulhameed Odhar , Safaa Muhsen Kareem , Mohammed Ridha A Alhaideri , Mohammed Abbas Hasan , Werner J Geldenhuys
Abstract
Parkinson’s disease is an age related neurodegenerative disease. Pioglitazone is a Peroxisome proliferator-activated
receptor gamma agonist that has been shown to display a neuroprotective effect in parkinsonian models (1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine treated mice). This effect was partially attributed to the ability of thiazolidinedione
(TZD) moiety in Pioglitazone to selectively inhibit monoamine oxidase B (MAO-B) enzyme. In the current study, we
screened several thiazolidine containing compounds against MAO-B enzyme both in silico and in vitro. Based on the
resulted data and information from previous literatures, we were able to design a novel scaffold for MAO-B inhibitors.
This scaffold (compound 5482440) was able to inhibit MAO-B enzyme with IC50 value of 1.447 µM. Structure-based
virtual analysis showed that this compound was able to participate in water-bridge formation and obtain an extended
conformation within MAO-B active site
Abstract
Parkinson’s disease is an age related neurodegenerative disease. Pioglitazone is a Peroxisome proliferator-activated
receptor gamma agonist that has been shown to display a neuroprotective effect in parkinsonian models (1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine treated mice). This effect was partially attributed to the ability of thiazolidinedione
(TZD) moiety in Pioglitazone to selectively inhibit monoamine oxidase B (MAO-B) enzyme. In the current study, we
screened several thiazolidine containing compounds against MAO-B enzyme both in silico and in vitro. Based on the
resulted data and information from previous literatures, we were able to design a novel scaffold for MAO-B inhibitors.
This scaffold (compound 5482440) was able to inhibit MAO-B enzyme with IC50 value of 1.447 µM. Structure-based
virtual analysis showed that this compound was able to participate in water-bridge formation and obtain an extended
conformation within MAO-B active site
Publication Date
6/1/2019
Publisher
International Journal of Pharmaceutical Quality Assurance
محمد عباس حسن | Mohammed Abbas Hasan | 14152