Aloke Dutta, Ph.D.

Aloke Dutta, Ph.D.

Adjunct Professor of Pharmacology

adutta@wayne.edu

Aloke Dutta, Ph.D.

Office Address

259 Mack Ave

3128 EACPHS, Detroit, MI

Office Phone

313-577-1064

Office Fax

313-577-2033

Biography

Our research integrates medicinal chemistry, neuropharmacology, computational chemistry and molecular biology not only to understand the mechanism of action of novel CNS active molecules but also to advance promising leads to preclinical studies. We focus on discovery of novel CNS drugs to explore their potential therapeutic application in several neuro-disorders like Parkinson’s disease (PD), depression and drug addiction. Specifically, novel molecules which are designed through rational drug design and computational studies, are being developed routinely to target monoamine transporters and receptors systems either selectively or non-selectively to produce desired pharmacological response. In PD research area we are focused on development of bi or polyfunctional molecules to produce disease modifying neuroprotective treatment agents. In this regard, we are designing multifunctional D2/D3 and D3 preferring agonists by incorporating metal chelation and anti-oxidant properties along with inhibitory activity against alpha-synuclein protein aggregation in these molecules to address complex pathogenesis of PD including oxidative stress. Our overall goal in this project is not only to address symptomatic (relieving motor dysfunction) factor of this disease but also to produce disease modifying neuroprotective effects to slow or stop the progression of the disease. In the depression area, we have developed novel triple uptake inhibitors as promising new generation antidepressants addressing anhedonia in MDD. One of our main thrust in our research is to develop multifunctional molecules as a novel approach to CNS drug discovery and development. Our research is supported by multiple NIH R01 grants.

Education

B.Sc. (Chemistry), 1983, University of Calcutta

Ph.D. (Organic Chemistry), 1987, Ohio University

Post-doctoral Associate (Bioorganic Chemistry), 1988-1991, University of Minnesota

Areas of Expertise

Medicinal Chemistry, CNS drug discovery, Neuropharmacology, Neurodegeneration, Neuropsychiatry

Areas of Interest

CNS drug discovery and development

Areas of Research

Medicinal Chemistry, CNS drug discovery, Neuropharmacology, Neurodegeneration, Neuropsychiatry

Grants

1. NIH/NINDS:
Title of the proposal: Novel neuroprotective treatment for Parkinson’s Disease
Duration: 09/15/11- 6/30/17
Principal Investigator: Aloke K. Dutta, Ph.D.

2. Title: TRIPLE UPTAKE INHIBITORS AS NOVEL ANTIDEPRESSANT
NIH/NIMH
Funding Period: 07/01/2009 to 06/30/2015
Principal Investigator: Aloke K. Dutta, Ph.D.

3. 7 R01 DA13261-06
Funding period: 09/01/2006 – 08/31/2011
Co-Investigator: Aloke K. Dutta, Ph.D.
NIH/NIDA: Dopamine transporters and ions, substrates, blockers

4. NIH/NIDA: "Dopamine transporter agents against cocaine dependence"
Duration: 09/25/2005 to 08/31/2009
P.I.: Aloke K. Dutta

5. NIH/NINDS:
Title of the proposal: Novel neuroprotective treatment for Parkinson’s Disease
Duration: 05/01/05-04/30/11
Principal Investigator: Aloke K. Dutta, Ph.D.

6. National Institutes of Health RO1 grant (NIH/NIDA)
Co-Investigator: Aloke K. Dutta, Ph.D.
Title of the Proposal: Affinity Labelling the Dopamine Transporter Active Site
Funding Period: 5/01/03-4/30/06

7. NIH/NIDA: "Dopamine transporter agents against cocaine dependence"
Duration: 12/1/99 to 11/30/2005
P.I.: Aloke K. Dutta

8. Wayne State University Faculty Research Grant #1-41824 awarded March 4, 1999. Title of proposal:
Design and Synthesis of Novel Nitric Oxide Synthase Inhibitors
P.I.: Aloke K. Dutta, Ph.D.
Duration: May 1, 1999 –April 30, 2000
 

9. NIH/NIDA: First Independent Research Support and Transition Award
"Potent and Selective Probes for the Dopamine Transporter."
Duration: 9/1/94 to 9/1/99
P.I: Aloke. K. Dutta

10. University of Minnesota, Minnesota Medical Foundation
"New D1 Specific Radioligands for the Central Nervous System".
Duration: 1989-1991.
P.I: Aloke K. Dutta


 

Publications

From 2012-Current

Juan Zhen, Solav Ali, Aloke K. Dutta, Maarten E.A. Reith. [3H]CFT can bind to the norepinephrine transporter with pharmacological relevance. J Neurosci Meth. 15; 203(1):19-27, 2012.

Novel bivalent ligands for D2/D3 dopamine receptors: Significant co-operative gain in D2 affinity and potency. Sanjib Gogoi, Swati Biswas, Antonio Tamara, Maarten Reith, Aloke Dutta. ACS Med Chem Lett. ;3(12):991-996, 2012.

Structural Exploration of (3S,6S)-6-Benzhydryl-N-benzyltetrahydro-2H-pyran-3-amine Analogues: Identification of Potent Triple Monoamine Reuptake Inhibitors as Potential Antidepressants.. Sanjib Gogoi, Soumava Santra, Bhaskar Gopishetty, Tamara Antonio, Juan Zhen, Maarten Reith, Aloke Dutta. ChemMedChem, 2012 Dec;7(12):2093-100

D-514, a multifunctional pro-drug with motor stimulating and neuroprotective properties: Possible neuroprotective treatment agent for Parkinson’s disease. Sanjib Gogoi, Asawari Lote, Tamara Antonio, Maarten Reith, Aloke Dutta. Manuscript in preparation.

Structure activity relationship study of N6-(2-(4-(1H-indol-5-yl)piperazin-1-yl)ethyl)-N6-propyl-4, 5, 6, 7-tetrahydrobenzo[d]thiazole-2, 6-diamine analogues: Development of highly selective D3 dopamine receptor agonists along with highly potent D2/D3 agonist and their pharmacological characterization. Mark Johnson, Tamara Antonio, Maarten Reith, Aloke Dutta. J. Med. Chem. 55, 5826-40, 2012.

Interaction of D3 preferring agonist (─)-N6-(2-(4-(Biphenyl-4-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264) with cloned human D2L, D2S and D3 receptors: Potent stimulation of mitogen-activated protein kinases and G-protein coupled inward rectifier potassium channels. Eldo Kuzhikandathil, Samantha Cote, Soumava Santra, Aloke K. Dutta. Naunyn-Schmiedeberg's Archives of Pharmacology, 386(2):97-105, 2013.

D-512 and D-440 as novel multifunctional dopamine agonists: Characterization of neuroprotection properties and evaluation of in vivo efficacy in a Parkinson’s disease animal model. Soumava Santra, Liping Xu, Mrudang Shah, Mark Johnson and Aloke Dutta. ACS Chem. Neurosci., 4 (10), pp 1382–1392, 2013.

Soumava Santra,1 Liping Xu,1 , Mark Johnson,1 Sanjib Gogoi,1 Tamara Antonio,2 Maarten E. A. Reith,2, Aloke K. Dutta1* (2013). . Approach towards development of multifunctional drugs as an effective strategy for treatment of Parkinson’s disease. In L. Eiden (Ed.), Catecholamine Research in the 21st Century: Abstracts and Graphical Abstracts, 10th International Catecholamine Symposium 2012, 148-149, Oxford, UK: Elsevier.

Bhaskar Gopishetty, Suhong Zhang, Prashant S. Kharkar, Tamara Antonio, Maarten Reith, Aloke K. Dutta. Modification of agonist binding moiety in hybrid derivative 5/ 7-{[2-(4-Aryl-piperazin-1-yl)-ethyl]-propyl-amino}-5,6,7,8-tetrahydro-naphthalen-1-ol/ -2-amino versions: Impact on functional activity and selectivity for dopamine D2/D3 receptors. Bioorganic & Medicinal Chemistry 21, 3164–3174, 2013.

Gyan Modi, Tamara Antonio, Maarten Reith, Aloke Dutta. Structural Modifications of Neuroprotective Anti-Parkinsonian (−)‑N6‑(2-(4-(Biphenyl-4-yl)piperazin-1-yl)-ethyl)‑N6‑propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine (D-264): An Effort toward the Improvement of in Vivo Efficacy of the Parent Molecule. J. Med. Chem. 2014, 57, 1557−1572.

High affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA induced apoptotic cell death and rescued dopaminergic neurons in the MPTP mouse model of Parkinson’s disease. Mrudang Shah, Chandrasekhar Voshavar, Liping Xu, Subramanian Rajagopalan, Julie Andersen, Aloke Dutta. Journal of Neurochemistry. Volume 131, Issue 1, 74–85, 2014.

Flexible and biomimetic analogs of triple uptake inhibitor 4-((((3S,6S)-6-benzhydryltetrahydro-2H-pyran-3-yl)amino)methyl)phenol : Synthesis, biological characterization, and development of a pharmacophore model Horrick Sharma,1 Soumava Santra,1 Joy Debnath,1 Bhaskar Gopishetty,1 Tamara Antonio,2 Maarten Reith,2,3 and Aloke Dutta1*. Bioorganic & Medicinal Chemistry 22 (2014) 311–324.

Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: Modulator of toxicity of Alpha synuclein aggregates. Gyan Modi, Chandrashekhar Voshavar, Mrudang Shah, Tamara Antonio, Maarten Reith, Aloke Dutta. ACS Chem. Neurosci., 2014, 5 (8), pp 700–717.

Pharmacological and behavioral characterization of an orally active triple reuptake inhibitor D-473: Effects of drug on extracellular levels of dopamine, serotonin and norepinephrine. Aloke Dutta, Soumava Santra, Horrick Sharma, Chandrasekhar Voshavar, Liping Xu, Omar Mabrouk, Tamara Antonio, Maarten Reith. Plos One, 2014, 9, e113420.

Development of potent dopamine-norepinephrine uptake inhibitors (DNRIs) based on (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol molecular template. Soumava Santra, Horrick Sharma, Seenuvasan Vedachalam, Tamara Antonio, Maarten Reith, Aloke Dutta. Bioorganic & Medicinal Chemistry, Volume 23, Issue 4, 15 2015, 821-828.

Dopamine D3 agonists in the Treatment of Parkinson's Disease. Banibrata Das, Gyan P. Modi, Aloke K. Dutta. Current Topics in Medicinal Chemistry, 15 (10), 908-926, 2015.

Assessment of protective role of multifunctional dopamine agonist D-512 against Oxidative stress produced by depletion of Glutathione in PC12 cells: Implication in neuroprotective therapy for Parkinson’s disease. Chandrasekhar Voshavar, Mrudang Shah, Liping Xu, Aloke Dutta. Neurotoxicity Research, 1-17, 2015.

Development of potent dopamine-norepinephrine uptake inhibitors (DNRIs) based on (2S,4R,5R)-2-benzhydryl-5-((4-methoxybenzyl)amino)tetrahydro-2H-pyran-4-ol molecular template. Soumava Santra, Horrick Sharma, Seenuvasan Vedachalam, Tamara Antonio, Maarten Reith, Aloke Dutta. Bioorganic & Medicinal Chemistry, Volume 23, Issue 4, 15 2015, 821-828.

Triple Uptake Inhibitor as a potential new generation antidepressant agents. Soumava Santra, Horrick Sharma and Aloke Dutta. Manuscript submitted (Invited Review). Future Med Chem. 2015 Nov; 7(17):2385-406.

Development of a Highly Potent D2/D3 Agonist and a Partial Agonist from Structure-Activity Relationship Study of N6-(2-(4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine Analogues: Implication in the Treatment of Parkinson’s Disease. Banibrata Das, Seenuvasan Vedachalam, Dan Luo, Liping Xu, Tamara Antonio, Maarten Reith, Aloke K. Dutta. J. Med. Chem. 2015, 58, 9179−9195

Efficacy of hybrid tetrahydrobenzo[d]thiazole based aryl piperazines D-264 and D-301at D2 and D3 receptors. Juan Zhen, Tamara Antonio, , Aloke K. Dutta, Dana Salley, Maarten E.A. Reith. Neurochemical Research, 2016 Feb;41(1-2):328-39.

Synthesis and Characterization of Brain Penetrant Prodrug of Neuroprotective D-264: Potential Therapeutic Application in the Treatment of Parkinson’s Disease. Fahd Dholkawala, Chandrashekhar Voshavar, Aloke K. Dutta, Journal of Pharmaceutics and Biopharmaceutics, 2016. 103, 62–70.

Inhibition of alpha-synuclein aggregation by multifunctional dopamine agonists assessed by a novel in vitro assay and an in vivo Drosophila synucleinopathy model. Deepthi Yedlapudi, Gnanada Joshi, Dan Luo, Sokol Todi, Aloke K. Dutta. Scientific Reports 6, Article number: 38510 (2016) doi:10.1038/srep38510.

Novel multifunctional dopamine D2/D3 receptors agonists as modulator of aggregation of alpha synuclein protein with potential neuroprotective property. Dan Luo, Horrick Sharma, Deepthi Yedlapudi, Tamara Antonio, Maarten E.A. Reith, Aloke K. Dutta, Bioorganic & Medicinal Chemistry, 2016, 24, 5088–5102.

 

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Department of Pharmacology