Aloke Dutta Ph.D,

Aloke Dutta Ph.D,

Title

Professor

Department

Pharmaceutical Sciences

Office Location

EACPHS, Room 3128

Phone

313-577-1064

Email

adutta@wayne.edu

Aloke Dutta Ph.D,

Degrees and Certifications

  • 1987, Doctor of Philosophy, Organic Chemistry, Ohio University, Athens (Minor in Biochemistry and Inorganic Chemistry)
  • 1981, Master of Science, Organic Chemistry, Calcutta University, Calcutta (Minor in Inorganic and Physical Chemistry)

Awards and Honors

GRANT AWARDS

1. NIH/NINDS:
Title of the proposal: Novel neuroprotective treatment for Parkinson’s Disease
Duration: 09/15/11- 6/30/16
Principal Investigator: Aloke K. Dutta, Ph.D.

2. Title: TRIPLE UPTAKE INHIBITORS AS NOVEL ANTIDEPRESSANT
NIH/NIMH
Funding Period: 07/01/2009 to 06/30/2014
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

Michigan Universities Commercialization Initiative (MUCI) Application

1. Title: Manufacture and Score 2000 Testing of WSU CNS Compounds (Dopamine Transporter Inhibitors) for use as a wake-cognition therapies
Research will be carried out with Hypnion, Inc, Worcester, MA
Principal Investigator: Aloke K. Dutta, Ph.D.
Funding period: July 2004 to August 2005

2. Title: Novel D3 receptor compounds (evaluation for application in Parkinson’s Disease)
Principal Investigator: Aloke K. Dutta, Ph.D.
Funding period: Q3 2004 to Q1 2006

3. Title: Triple Monoamine Reuptake Inhibitor as New Generation Antidepressants
Principal Investigator: Aloke K. Dutta, Ph.D.
Funding period: Q4 2008 to Q4 2009

Professional Memberships

Editorial Board Member

  • Editorial board membership of the journal Current Medicinal Chemistry-Central Nervous System.
  • Editorial board membership of the journal The open bioactive compounds journal.
  • Editorial board membership of the journal “Neurotransmitter.

Member of NIH/NIDA Study Sections

  • Standing committee member of NIH/NIDA “Medication Development Research Subcommittee , 2007-2011.
  • Ad hoc member of “Molecular Neuropharmacology and Signaling Study Section (MNPS) study section, 2009-2010.
  • Ad hoc member of “Drug Discovery for the Nervous System, ZRG1 MDCN-C 91 study section, 2009-2012.
  • Standing committee member of DDNS “Drug Discovery for the Nervous System 2012-2014.
  • Standing committee member of Molecular Probes,ZRG1 MDCN-C (58) 2012-2014.
  • Ad hoc member of “Drug Discovery for the Nervous System, ZRG1 MDCN-C (94) study section, 2015.
  • 
Reviewer of Research Corporation: A foundation for advancement of science



Standing Committee Member of NIH Study Section

  • Standing committee member of NIH/NIDA Medication Development Research Subcommittee , 2007-2011



Journal Reviewer

  • Reviewer of Journal of Medicinal Chemistry.

  • Reviewer of Bioorganic and Medicinal Chemistry Letters.

  • Reviewer of Bioorganic and Medicinal Chemistry.

  • Reviewer of Medicinal Chemistry Research

  • Reviewer of Current Medicinal Chemistry-Central Nervous System Agents

  • Reviewer, Australian Journal of Chemistry
Reviewer, Drug and alcohol dependence

  • Reviewer, European Journal of Medicinal Chemistry

  • Current Topics in Medicinal Chemistry

  • Tetrahedron

  • Biochemical Pharmacology
  • 
British Journal of Pharmacology

  • Archive der Pharmazie

Primary Research Interest

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 has been supported by multiple NIH R01 grants.

Recent Publications

Peer Reviewed Publications/ Patents (from a total of 130)

The multifunctional dopamine D2/D3 receptors agonists with inhibitory activity against the full-length tau441 aggregation. Iva Ziu, Irving Rettig, Dan Luo, Aloke K. Dutta, Theresa M. McCormick,2and Sanela Martic-Milne. Accepted in Bioorganic Medicinal Chemistry, 2020.

Design, Synthesis and Pharmacological Characterization of Carbazole Based Dopamine Agonists as Potential Symptomatic and Neuroprotective Therapeutic Agents for Parkinson's Disease. Asma Elmabruk, Banibrata Das, Liping Xu,Tamara Antonio, Maarten E.A. Reith, Aloke K. Dutta. ACS Chemical Neuroscience. ACS Chem Neurosci. 2019 Jan 16;10(1):396-411.
Targeting alpha synuclein protein and amyloid beta by a multifunctional brain penetrant dopamine D2/D3 agonist D-520: Potential therapeutic application in Parkinson's disease with dementia. Deepthi Yedlapudi, Liping Xu, Sokol Todi, Aloke Dutta. Scientific Reports, 2019 Dec 23;9(1):19648.
D-578, an orally active triple monoamine reuptake inhibitor, displays antidepressant and anti-PTSD like effects in rats. Aloke K. Dutta, Soumava Santra, Arman Harutyunyan, Banibrata Das, Michael Lisieski, Liping Xu, Tamara Antonio, Maarten E.A. Reith, Shane A. Perrine. European Journal of Pharmacology. 2019 Nov 5; 862: 172632.
A Novel Orally Active Triple Reuptake Inhibitor for the Treatment of Post-Traumatic Stress Disorder (PTSD): D-578 Attenuates Abnormal Fear Behavior in a Rodent Model of Traumatic Stress. Michael Lisieski, Arman Harutyunyan, Banibrata Das, Israel Liberzon, Frank P. Bymaster, Timothy Hsu, Maarten Reith, Shane A. Perrine, Aloke K. Dutta. Biological Psychiatry, 85(10):S216 · May 2019.
Alpha-synuclein aggregation modulation: An emerging approach for the treatment of Parkinson's disease. Sushil K. Singh, Aloke Dutta, and Gyan Modi. Invited Review, Future Medicinal Chemistry, 9(10):1039-1053, 2017.
D-512, a novel dopamine D2 / D3 receptor agonist, demonstrates superior anti-parkinsonian efficacy over ropinirole in parkinsonian rats. David Lindenbach, Banibrata Das, Melissa M. Conti, Samantha Meadows, Aloke K. Dutta, Christopher Bishop. British Journal of Pharmacology, 174(18):3058-3071, 2017.
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy Stemmler, Maarten Reith, Aloke Dutta. A novel iron(II) preferring dopamine agonist chelator as potential symptomatic and neuroprotective therapeutic agent for Parkinson's disease. ACS Chem. Neurosci. 2017, 8, 723-730.
Banibrata Das, Subramanian Rajagopalan, Gnanada S. Joshi, Liping Xu, Dan Luo, Julie K. Andersen, Sokol V. Todi, Aloke K. Dutta. A novel iron (II) preferring dopamine agonist chelator D-607 significantly suppresses α-syn- and MPTP-induced toxicities in vivo. Neuropharmacology. 2017, 123, 88-99.
Juan Zhen, Tamara Antonio, Aloke K. Dutta, Dana Salley, Maarten E.A. Reith. Efficacy of hybrid tetrahydrobenzo[d]thiazole based aryl piperazines D-264 and D-301 at D2 and D3 receptors. Neurochemical Research, 2016, 41(1-2), 328-39.
Fahd Dholkawala, Chandrashekhar Voshavar, Aloke K. Dutta. Synthesis and characterization of brain penetrant prodrug of neuroprotective D-264: Potential therapeutic application in the treatment of Parkinson's disease. J. Pharmaceutics and Biopharmaceutics, 2016, 103, 62–70.
Deepthi Yedlapudi, Gnanada Joshi, Dan Luo, Sokol Todi, Aloke K. Dutta. Inhibition of alpha-synuclein aggregation by multifunctional dopamine agonists assessed by a novel in vitro assay and an in vivo Drosophila synucleinopathy model. Scientific Reports 6, Article number: 38510 (2016). doi:10.1038/srep38510.
Dan Luo, Horrick Sharma, Deepthi Yedlapudi, Tamara Antonio, Maarten E.A. Reith, Aloke K. Dutta. Novel multifunctional dopamine D2/D3 receptors agonists as modulator of aggregation of alpha synuclein protein with potential neuroprotective property. Bioorganic & Medicinal Chemistry, 2016, 24, 5088–5102.
Soumava Santra, Horrick Sharma, Seenuvasan Vedachalam, Tamara Antonio, Maarten Reith, Aloke Dutta. 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. Bioorg. Med. Chem. 2015, 23, 821-828.
Banibrata Das, Gyan P. Modi, Aloke K. Dutta. Dopamine D3 agonists in the Treatment of Parkinson's Disease. Curr. Top. Med. Chem., 2015, 15(10), 908-926.
Juan Zhen, Tamara Antonio, Solav Ali, Kim A. Neve, Aloke K. Dutta, Maarten E.A. Reith. Use of radiolabeled antagonist assays for assessing agonism at D2 and D3 dopamine receptors: Comparison with functional GTPγs assays. J. Neurosci. Methods. 2015, 248, 7-15.
Chandrasekhar Voshavar, Mrudang Shah, Liping Xu, Aloke Dutta. 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. Neurotoxicity Research, 2015, 1-17.
Soumava Santra, Horrick Sharma, Aloke Dutta. Triple Uptake Inhibitor as a potential new generation antidepressant agents. Future Med. Chem. 2015, 7(17), 2385-2406.
Banibrata Das, Seenuvasan Vedachalam, Dan Luo, Tamara Antonio, Maarten Reith, Aloke Dutta. Development of a highly potent D2/D3 agonist and a partial agonist from structure-activity relationship study of N(6)-(2-4-(1H-Indol-5-yl)piperazin-1-yl)ethyl)-N(6)-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine analogues: Implication in the treatment of Parkinson's disease. J. Med. Chem. 2015, 58(23), 9179-9195.
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.
Mrudang Shah, Chandrasekhar Voshavar, Liping Xu, Subramanian Rajagopalan, Julie Andersen, Aloke Dutta. 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. J. Neurochem. 2014, 131, 74–85.
Horrick Sharma, Soumava Santra, Joy Debnath, Bhaskar Gopishetty, Tamara Antonio, Maarten Reith, Aloke Dutta. 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. Bioorg. Med. Chem. 2014, 22, 311–324.
Gyan Modi, Chandrashekhar Voshavar, Mrudang Shah, Tamara Antonio, Maarten Reith, Aloke Dutta. Multifunctional D2/D3 agonist D-520 with high in vivo efficacy: Modulator of toxicity of Alpha synuclein aggregates. ACS Chem. Neurosci. 2014, 5, 700–717.
Gyan Modi, Horrick Sharma, Prashant S. Kharkar, Aloke Dutta. Understanding the structural requirements of hybrid (S)-6-((2-(4-phenylpiperazin-1-yl)ethyl)(propyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol and its analogs as D2/D3 receptor ligands. A three-dimensional quantitative structure-activity relationship (3D QSAR) investigation. Medchemcomm. 2014, 5(9), 1384-1399.
Aloke Dutta, Soumava Santra, Horrick Sharma, Chandrasekhar Voshavar, Liping Xu, Omar Mabrouk, Tamara Antonio, Maarten Reith. Pharmacological and behavioral characterization of an orally active triple reuptake inhibitor D-473: Effects of drug on extracellular levels of dopamine, serotonin and norepinephrine. PLoS One, 2014, 9, e113420.
Eldo Kuzhikandathil, Samantha Cote, Soumava Santra, Aloke K. Dutta. 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. Naunyn-Schmiedeberg's Archives of Pharmacology, 2013, 386(2), 97-105.
Soumava Santra, Liping Xu, Mrudang Shah, Mark Johnson, Aloke Dutta. 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. ACS Chem. Neurosci. 2013, 4(10), 1382–1392.
Soumava Santra, Liping Xu, Mark Johnson, Sanjib Gogoi, Tamara Antonio, Maarten E. A. Reith, Aloke K. Dutta. (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. Bioorg. Med. Chem. 2013, 21, 3164–3174.

 

List of Patents

1. Dutta, A. K. NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES, U.S. Patent No. 10,125,127, November 13, 2018.

2. Dutta, A. K. TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OLANALOGUES, AND NOVEL 3,6 DISUBSTITUTED PYRAN DERIVATIVES. Canadian Pat No, 2563161, January 24, 2017.

3. Dutta, A. K. Substituted pyran derivatives, US 9458124 B2, approved on Oct 4, 2016.

4. Dutta, A. K. Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives. U.S. Pat. No. US 8,937,189, January 20, 2015.

5. Dutta, A. K. Bifunctional/polyfunctional dopamine D2/D3 agonist as neuroprotective agents for treatment of neurodegenerative diseases, U.S. Pat. No. US 9,034,877, May 19, 2015.

6. Dutta, A. K. "TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES". European Pat. No. EP 1 734948 B1, June 11, 2014.

7. Dutta, A. K. Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives. U.S. Pat. No. US 8,841,464, September 23, 2014.

8. Dutta, A. K. "Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.", WSU 0203PUSA, U.S. Pat. No. US8,519,159 B2, August 27, 2013.

9. Dutta, A. K. "TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OL ANALOGUES, AND NOVEL 3,6-DISUBSTITUTED PYRAN DERIVATIVES". European Pat. No. EP 1 976 381 B1, July 24, 2013.

10. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY. PATENT NO: US 8,227,604 B2, July 24, 2012.

11. Dutta, A. K. N- and O-substituted 4-[2-(diphenylmethoxy)-ethyl]-1-[(phenyl)methyl]piperidine analogs and methods of treating CNS disorders therewith, U.S. Pat. No. US 8,211,916, July 3, 2012.

12. Dutta, A. K. "Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.", WSU 0203PUSA, U.S. Pat. No. US8,017,791, September 13, 2011.

13. Dutta, A. K . TRI-SUBSTITUTED 2-BENZHYDRYL-5-BENZLAMINO-TETRAHYDRO-PYRAN-4-OL AND 6-BENZHYDRYL-4-BENZYLAMINO-TETRAHYDRO-PYRAN-3-OLANALOGUES, AND NOVEL 3,6 DISUBSTITUTED PYRAN DERIVATIVES. U.S. Pat. No. US 7915433, April 4, 2011.

14. Dutta, A. K. "Tri-substituted 2-benzhydryl-5-benzylamino-tetrahydro-pyran-4-ol and 6-benzhydryl-4-benzylamino-tetrahydro-pyran-3-ol analogues, and novel 3,6-disubstituted pyran derivatives.", WSU 0203PUSA, U.S. Pat. No. US7,915,433 B2, March 29, 2011.

15. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY. U.S. Patent Appn. No. 11/235612 (WSU 0197 PUSA1). Status: Patented as U.S. Pat. No. 7,723,519. Issue Date: May 25, 2010.

16. N-AND O-SUBSTITUTED 4-[2-( DIPHENYLMETHOXY) -ETHYL]-1- (PHENYL) METHYL) PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH. U.S. Pat. No. 7,595,331, September 29, 2009.

17. N- AND O-SUBSTITUTED 4-[2-(DIPHENYLMETHOXY)-ETHYL]-1-(PHENYL) METHYL) PIPERIDINE ANALOGS AND METHODS OF TREATING CNS DISORDERS THEREWITH. PATENT NO: US 6,995,268 B2; FEBRUARY 7 2006.

18. HYBRID 2-AMINOTETRALIN AND ARYL-SUBSTITUTED PIPERAZINE COMPOUNDS AND THEIR USE IN ALTERING CNS ACTIVITY. PATENT NO: US 6,982,332, JANUARY 3, 2006.

19. Derivatives of 2-aminotetralins and pharmaceutical analogs thereof exhibiting differentail cns receptor activity and behavior. Patent NO: US 7049337 B2; May 23, 2006.

 


 

 

Laboratory Web Site

The Dutta Group