This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The main goal of this project is to continue developing novel organic synthetic methodology for the preparation of potential nicotinic receptor agonist that will be valuable for the treatment of neuron-degenerative diseases, such Alzheimer and Parkinson, schizophrenia, attention deficit/hyperactivity and Tourette's syndrome and in the treatment of nicotine addition. In general, our work will focus on four major research areas: 1) development of new methodology for the asymmetric synthesis of biological important pyridyl and heterocyclic amino derivatives using our recently developed spiroborate catalysts for the reduction of ketones and oxime ethers;2) design and synthesized novel chiral nicotinic analogs and of chiral drugs for neurodegenerative diseases;3) biological testing of the new synthesized compounds as nicotinic receptor agonist, acetyl cholinesterase inhibitors and possibly, with antioxidant properties carried out in Dr. Lasalde Neurobiology Laboratory at UPR, Biology Department;and 4) study the structural factors affecting the reactivity and stereochemistry of the catalysts in the proposed synthetic methodology, in addition to the structure-activity studies that will be addressed by the CoPI, Dr. Carmelo Garcia, from UPR-Humacao using Gaussian 03 or Spartan 2.0 chemical computational methods. The results on this proposed interdisciplinary project on the search for new method for potential new nAChRs agonist are expected to strengthen our research capability for the submission of an RO1 proposal.
Specific Aims : 1) To investigate the borane-mediated reduction of prochiral multifunctional ketones and oximes using spiroborate reagents and study their transformation to more complex chiral amino ethers, amino alcohols and diamino compounds. 2) To explored the use of spiroborate ester catalyst for the asymmetric reduction of model A/-substitute imines. 3) To establish protocols for the synthesis of novel alcohols and amino derivatives as nicotinic receptor agonist with multifunctional neuronal functions. 4) To test the new amino compounds as potential agonists for neuronal nicotinic receptors (nAChRs) and cholinesterase inhibitors using voltage clamp techniques and recombinant expression of nAChRs in oocytes and its electrophysiological characterization at mice neuromuscular junction. 5) To establish the optimal stereochemistry of chiral reagents and transition states for the proposed enantioselective reactions using molecular modeling methods. Molecular modeling will also be used to study the correlation between agonist's structure and observed and calculated affinities for the nACH receptors.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016470-11
Application #
8360150
Study Section
Special Emphasis Panel (ZRR1-RI-4 (01))
Project Start
2011-06-01
Project End
2012-05-31
Budget Start
2011-06-01
Budget End
2012-05-31
Support Year
11
Fiscal Year
2011
Total Cost
$103,464
Indirect Cost
Name
University of Puerto Rico Rio Piedras
Department
Type
DUNS #
090051616
City
San Juan
State
PR
Country
United States
Zip Code
00926
Cantres-Rosario, Yisel M; Acevedo-Mariani, Frances M; Pérez-Laspiur, Juliana et al. (2017) Microwave & magnetic proteomics of macrophages from patients with HIV-associated cognitive impairment. PLoS One 12:e0181779
Mariño, Yobana A; Verle Rodrigues, José C; Bayman, Paul (2017) Wolbachia Affects Reproduction and Population Dynamics of the Coffee Berry Borer (Hypothenemus hampei): Implications for Biological Control. Insects 8:
Martínez-Rivera, Freddyson J; Pérez-Laspiur, Juliana; Santiago-Gascot, María E et al. (2017) Differential protein expression profile in the hypothalamic GT1-7 cell line after exposure to anabolic androgenic steroids. PLoS One 12:e0180409
Zenón, Frances; Jorge, Inmaculada; Cruz, Ailed et al. (2016) 18O proteomics reveal increased human apolipoprotein CIII in Hispanic HIV-1+ women with HAART that use cocaine. Proteomics Clin Appl 10:144-55
Rivera-Rivera, Yainyrette; Vázquez-Santiago, Fabián J; Albino, Elinette et al. (2016) Impact of Depression and Inflammation on the Progression of HIV Disease. J Clin Cell Immunol 7:
Martínez-Rivera, Freddyson J; Rodriguez-Romaguera, Jose; Lloret-Torres, Mario E et al. (2016) Bidirectional Modulation of Extinction of Drug Seeking by Deep Brain Stimulation of the Ventral Striatum. Biol Psychiatry 80:682-690
Suárez-Arroyo, Ivette J; Rios-Fuller, Tiffany J; Feliz-Mosquea, Yismeilin R et al. (2016) Ganoderma lucidum Combined with the EGFR Tyrosine Kinase Inhibitor, Erlotinib Synergize to Reduce Inflammatory Breast Cancer Progression. J Cancer 7:500-11
Suárez-Arroyo, Ivette J; Feliz-Mosquea, Yismeilin R; Pérez-Laspiur, Juliana et al. (2016) The proteome signature of the inflammatory breast cancer plasma membrane identifies novel molecular markers of disease. Am J Cancer Res 6:1720-40
Wang, Hai-Yang; Huang, Kun; De Jesús, Melvin et al. (2016) Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water. Tetrahedron Asymmetry 27:91-100
Colon, Krystal; Perez-Laspiur, Juliana; Quiles, Raymond et al. (2016) Macrophage secretome from women with HIV-associated neurocognitive disorders. Proteomics Clin Appl 10:136-43

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