title: Therapeutic, Molecular and Computational Aspects of Novel Monoamine Oxidase (MAO) Inhibitors.
abstract: Background Due to the limited number of MAO inhibitors in the clinics, several research efforts are aimed at the discovery of novel MAO inhibitors. At present, a 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 of drug.
  
  
  OBJECTIVE
  Most of the existing MAO inhibitors lead to side effects due to the 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. Hence, MAO-A inhibitors 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. The present study was aimed to describe the recently developed hits of MAO inhibitors.
  
  
  METHODS
  At present, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban- 4001. South Africa.
authors.forename: Muthusamy
authors.initials: M
authors.lastname: Ramesh
authors.affiliation: Molecular Modeling and Drug Design Research Group, College of Pharmacy and Pharmaceutical Science Research Center, Florida Agricultural and Mechanical University (FAMU), Tallahassee, Florida 32307. United States.
authors.forename: Yussif M
authors.initials: YM
authors.lastname: Dokurugu
authors.affiliation: Molecular Modeling and Drug Design Research Group, College of Pharmacy and Pharmaceutical Science Research Center, Florida Agricultural and Mechanical University (FAMU), Tallahassee, Florida 32307. United States.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Thompson
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Westville, Durban- 4001. South Africa.
authors.forename: Mahmoud E
authors.initials: ME
authors.lastname: Soliman
mesh_terms: D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase
keywords: Alzheimer's disease; MAO inhibition; Parkinson's disease; QSAR; computer-aided drug design; pharmacophore
  modeling