Journal article
Novel Potent Dopamine-Norepinephrine and Triple Reuptake Uptake Inhibitors Based on Asymmetric Pyran Template and Their Molecular Interactions with Monoamine Transporters
ACS chemical neuroscience, v 12(8), pp 1406-1418
21 Apr 2021
PMID: 33844493
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We have carried out a structural exploration of (2S,4R,5R)-2-(bis(4-fluorophenyl)methyl)-5-((4-methoxybenzyl) amino)tetrahydro-2H-pyran-4-ol (D-473) to investigate the influence of various functional groups on its aromatic ring, the introduction of heterocyclic aromatic rings, and the alteration of the stereochemistry of functional group on the pyran ring. The novel compounds were tested for their affinities for the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) in the brain by measuring their potency in inhibiting monoamine neurotransmitter uptake. Our studies identified some of the most potent dopamine-norepinephrine reuptake inhibitors known to-date like D-528 and D-529. The studies also led to development of potent triple reuptake inhibitors such as compounds D-544 and D-595. A significant influence from the alteration of the stereochemistry of the hydroxyl group on the pyran ring of D-473 on transporters affinities was observed indicating stereospecific preference for interaction. The inhibitory profiles and structure-activity relationship of lead compounds were further corroborated by molecular docking studies at the primary binding sites of monoamine transporters. The nature of interactions found computationally correlated well with their affinities for the transporters.
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Details
- Title
- Novel Potent Dopamine-Norepinephrine and Triple Reuptake Uptake Inhibitors Based on Asymmetric Pyran Template and Their Molecular Interactions with Monoamine Transporters
- Creators
- Soumava Santra - Wayne State UniversitySandhya Kortagere - Drexel UniversitySeenuvasan Vedachalam - Wayne State UniversitySanjib Gogoi - Wayne State UniversityTamara Antonio - New York UniversityMaarten E. A. Reith - New York UniversityAloke K. Dutta - Wayne State University
- Publication Details
- ACS chemical neuroscience, v 12(8), pp 1406-1418
- Publisher
- American Chemical Society; Washington, DC
- Number of pages
- 13
- Grant note
- DA019676 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA MH084888 / National Institute of Mental Health/The National Institute of Health
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000643598600012
- Scopus ID
- 2-s2.0-85105055425
- Other Identifier
- 991019167875804721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Chemistry, Medicinal
- Neurosciences