M Ramesh , Yussif M. Dokurugu, Michael D. Thompson and Mahmoud Soliman Pages 1 - 18 ( 18 )
Due to the limited number of MAOs inhibitors in the clinic and several research efforts are aimed at the discovery of novel MAOs inhibitors. At present, high specificity and a reversible mode of inhibition of MAO-A/B are cited as desirable traits in drug discovery process. This will help to reduce the probability of causing target disruption and may increase the duration of action. Most of the existing MAO inhibitors lead to side effects due to lack of affinity and selectivity. Therefore, there is an urgent need to design novel, potent, reversible and selective inhibitors for MAO-A/B. Selective inhibition of MAO-A results in the elevated level of serotonin and noradrenaline and can be used for improving the symptoms of depression. The selective MAO-B inhibitors are used with L-DOPA and/or dopamine agonists in the symptomatic treatment of Parkinson’s disease. Recently, CADD techniques are gaining an attention in rationale drug discovery of MAO inhibitors, and several research groups employed CADD approaches on various chemical scaffolds to identify novel MAO inhibitors. These computational techniques assisted in the development of lead molecules with improved pharmacodynamics / pharmacokinetic properties toward MAOs. Further, CADD techniques provided a better understanding of structural aspects of molecular targets and lead molecules. The present review describes the importance of structural features of potential chemical scaffolds as well as the role of computational approaches like ligand docking, molecular dynamics, QSAR and pharmacophore modeling in the development of novel MAO inhibitors.
MAO inhibition, Parkinson’s disease, Alzheimer`s diseases, Computer-aided drug design
Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban-4001, Molecular Modeling and Drug Design Research Group, College of Pharmacy and Pharmaceutical Science Research Center, Florida Agricultural and Mechanical University (FAMU), Tallahassee, Florida, 32307, Molecular Modeling and Drug Design Research Group, College of Pharmacy and Pharmaceutical Science Research Center, Florida Agricultural and Mechanical University (FAMU), Tallahassee, Florida, 32307, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban-4001