Novel Cholinergics for Treatment of Central Nervous System Disorders Item Type dissertation Authors Johnson, Chad Publication Date 2019 Abstract Approximately 16% of Americans are diagnosed with major depressive disorder, a mental disorder thought be caused by a combination of characterized by genetic, biological, environmental, and psychological factors. It can be accompanied by low self-est... Keywords Pharmaceutical sciences; behavioral pharmacology; medicinal chemistry; Antidepressive Agents; Chemistry, Pharmaceutical; Drug Design; Pharmacology; Receptors, Muscarinic Download date 07/10/2021 09:00:20 Link to Item http://hdl.handle.net/10713/11602 Curriculum Vitae NAME: Chad Johnson TITLE: Ph.D. Candidate Department of Pharmaceutical Sciences University of Maryland School of Pharmacy 20 N Pine St, Room N706 Baltimore, MD 21201 Phone: 410-706-1578 Email: [email protected] RESIDENT STATUS: USA Permanent Resident EDUCATION: B.S. Chemistry University of Virginia Charlottesville, VA 2005-2009 M.A. Chemistry (Organic/Bio-Organic) Johns Hopkins University Baltimore, MD 2009-2013 Ph.D. Candidate (Pharmaceutical Sciences) University of Maryland, Baltimore Baltimore, MD 2015-2019 TEACHING EXPERIENCE: UNIVERSITY OF MARYLAND, BALTIMORE Training course for departmental hydrogenator Training course for Advion Expression L benchtop Mass Spectrometer Weekly synthetic Chemistry group meetings Teaching Assistant for Medicinal Chemistry 1/2 and Infectious Disease Therapeutics 1/2 PHMY5008-Professional Communication Strategies MS in Medical Cannabis and Therapeutics-Instructor for MSMC 602 (Principles of Drug Action and Cannabinoid Pharmacology, Teaching Assistant for MSMC 601 (Introduction to Medical Cannabis History, Culture, and Policy) JOHNS HOPKINS UNIVERSITY Teaching Assistant Organic Chemistry and Organic Chemistry Laboratory 1/2 (August 2009-July 2014) UNIVERSITY OF VIRGINIA Teaching Assistant Organic Chemistry 1/2 Laboratory (August 2008-May 2009) PRIVATE TUTOR GRE, MCAT, and Organic Chemistry (August 2009- Current) HONORS/AWARDS: Finalist for Best Teaching Assistant Award (JHU, 2014) Finalist for Hertz Fellowship Award (UMB, 2016) Inducted into Rho Chi Honor Society (UMB, 2016) Travel Award for Behavior, Biology, and Chemistry (BBC) Translation Research in Addiction Conference (2017,2018, and 2019) Wal-Mart Scholar (UMB, American Association of Colleges of Pharmacy, 2019) PROFESSIONAL MEMBERSHIPS: American Chemical Society: Student Member 2009- Current American Association of Pharmaceutical Scientists: Student Member 2016-Current American Association of Colleges of Pharmacy: Student Member 2017-Current American Association for the Advancement of Science: Student Member: 2016-Current Rho Chi Honor Society: 2016-Current (Serve on Academic Committee) PUBLICATIONS: 1) Ansari, M. I.; Johnson, C.; Coop, A. PARP Inhibitors: A Breakthrough in Cancer Chemotherapy. Modern Approaches in Drug Design , 2(1), 2018. 2) Johnson, C.; Ansari, M. I.; Coop, A. Tetrabutylammonium Bromide Promoted Metal-Free, Efficient, Rapid, and Scalable Synthesis of N-Arylated Amines. ACS Omega. 2018, 3(9), 10886- 10890. 3) Saquib, M., Ansari, M. I., Johnson, C., Khatoon, S., Hussain, M. K., and Coop. A. Recent Advances in the Targeting of Human DNA Ligase 1 as a Potential New Strategy for Cancer Treatment. Eur. J. Med. Chem. 2019 , 182, 111657. PRESENTATIONS: 1. ACS National Meeting: Chemistry of the People, by the People, for the People . Philadelphia, PA. "Inhibitors of LHR-1 as Novel Anti-Parasitic Drugs." Poster Presentation, August 2016 . 2. UMD-JHU Joint Symposium on Drug Discovery : Baltimore, MD. Reinforcing Activity of Meta-Nicotine, Nicotine, and A8530. Poster Presentation. 2017 3. Behavior, Biology, and Chemistry: Translational Research in Addiction , San Antonio, TX. "Reinforcing Properties of Meta-Nicotine." Poster Presentation, Travel Awardee , 2017 . 4. School of Pharmacy Research Day : Baltimore, MD. "Comparisons of the Reinforcing Activity of Meta-Nicotine, Nicotine, and A8530." Poster Presentation, 2017 . 5. Frontiers in Chemistry and Biology Interface Symposium : Newark, DE. "Comparisons of the Reinforcing Activity of Meta-Nicotine, Nicotine, and A8530." Poster Presentation, May 2017. 6. Ph.D. Candidacy Public Seminar : Baltimore, MD. "Novel Cholinergics for Treatment of CNS Disorders." Oral Presentation, 2017 . 7. Behavior, Biology, and Chemistry: Translational Research in Addiction, San Antonio, TX. "Muscarinic Antagonists and Anti-depressant-like Effects in Rodents: Some Chemical Forays Toward New Compounds." Poster Presentation, Travel Awardee, 2018. 8. Graduate Research Conference: Baltimore, MD. "Muscarinic Antagonists and Anti- depressant-like Effects in Rodents: Some Chemical Forays Toward New Compounds." Poster Presentation, 2018 . 9. School of Pharmacy Research Day : Baltimore, MD. "Muscarinic Antagonists and Anti- depressant-like Effects in Rodents: Some Chemical Forays Toward New Compounds." Poster Presentation, 2018 . 10. Frontiers in Chemistry and Biology Interface Symposium : Philadelphia, PA. "Novel Muscarinic Antagonists: Design, Synthesis and Pharmacological Evaluation in Rodents." Poster Presentation, 2018 . 11. Computer Aided Drug Design Symposium , Baltimore, MD. "Novel Muscarinic Antagonists: Design, Synthesis and Pharmacological Evaluation in Rodents." Poster Presentation, 2018 . 12. American Association of Colleges of Pharmacy National Meeting , Boston, MA. "Mentoring Undergraduate Students in an Academic Research Laboratory: What to Know, What to Do, and What to Expect as a Graduate Student and Faculty Mentor." Poster Presentation. 2018 . 13. Behavior, Biology, and Chemistry: Translational Research in Addiction , San Antonio, TX. "Muscarinic Antagonists and Anti-depressant-like Effects in Rodents: Some Chemical Forays Toward New Compounds." Poster Presentation, Travel Awardee, 2018 . 14. School of Pharmacy Research Day : Baltimore, MD. "Muscarinic Antagonists and Anti- depressant-like Effects in Rodents: Methyl to Cyclopropyl." Poster Presentation, 2018 . 15. American Chemical Society Mid-Atlantic Regional Meeting : Baltimore, MD. "Novel Muscarinic Antagonists with Anti-Depressant-Like Effects in Rodents." Poster Presentation, 2019 . RESEARCH: UNIVERSITY OF MARYLAND, BALTIMORE Research Topic : Novel Cholinergics for Treatment of CNS Disorders Major depression is a widespread psychiatric disorder demonstrating severe symptoms in how a person feels, thinks, and handles daily activities (nih.gov). Furthermore, it is linked to diminished quality of life, medical morbidity, and mortality. Depression has a lifetime prevalence of 16% in the United States and appears to be caused by a combination of genetic, biological, environmental, and psychological factors. Current antidepression medications possess significant problems, including a delayed onset of action and different therapeutic effects in differing patients. As such, rapid acting fully efficacious antidepressants are urgently needed. Non- selective muscarinic antagonists have been shown to display antidepressant effects, but this is accompanied by undesired cognitive deficits. The hypothesis of this project is that antagonism of one or more muscarinic subtypes leads to an antidepressant effect, and antagonism at others lead to the cognitive deficits. As selective agonists and antagonists are not available for the 5 muscarinic receptor subtypes, we aim to design and synthesize-- using the scaffolds of L-670548, L-687306, WAY-132983, and L-689660 as model scaffolds-- muscarinic ligands to allow a delineation of the structure activity relationship (SAR) for both selectivity and efficacy, with the ultimate goal of a muscarinic antagonist lacking cognitive deficits. JOHNS HOPKINS UNIVERSITY (Graduate Research Assistant): • Constructed two total syntheses with optimization of all reactions to obtain novel β-methyl carbapenem antibiotics and various derivatives thereof. • Purified each novel compound via column chromatography or preparative HPLC Ran biological assays using these compounds and purified ThnQ/SarQ grown from bacterial cells over-expressing these proteins. • Constructed synthetic standards to compare the compounds produced from the above assays (2009-2013). UNIVERSITY OF VIRGINIA (Undergraduate Research Assistant): • Designed and successfully synthesized various derivatives of FTY720 (2008-2009) Abstract Title of Dissertation: Novel Cholinergics for Treatment of Central Nervous System Disorders Chad R. Johnson, Ph.D., 2019 Dissertation Directed by: Dr. Andrew Coop, Professor and Associate Dean for Academic Affairs, Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore Approximately 16% of Americans are diagnosed with major depressive disorder, a mental disorder thought be caused by a combination of characterized by genetic, biological, environmental, and psychological factors. It can be accompanied by low self-esteem, loss of interest in normally enjoyable activities, low energy, and diminished quality of life. Between 2- 7% of adults with this disorder die by suicide. In addition, almost half of patients who are treated initially with an SSRI do not achieve complete remission, and nearly a third after four different treatment regimens (nimh.nih.gov). While counseling and antidepressant medication can be effective treatments, current selective serotonin re-uptake inhibitors (SSRI's) take weeks before therapeutic effects are observed. This "delay" period of action is not well understood and presents a significant challenge for medical